Targeting glutamine metabolism exhibits anti-tumor effects in thyroid cancer.

BACKGROUND: Effective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer. METHODS: The expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography-mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice. RESULTS: GLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1. CONCLUSIONS: Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer.

[Cancer survival analysis in Tianjin, 2010 to 2016].

Objective: Survival analysis of cancers' incidence data in Tianjin from 2010 to 2016 was conducted to provide the basis for formulating and evaluating regional health policies on cancer prevention and treatment. Methods: Registration data in Tianjin were used between January 1, 2010 to December 31, 2016 and patients were followed-up till 31 December, 2021. Life-table method was used to calculate the observed survival rate and Edered Ⅱ was used to calculate the relative survival rate. The data were stratified by year, gender, age group and cancer sites. Difference in survival curves between group was analyzed by Kaplan-Meier method and Log rank test. Joinpoint regression model was used to analyze the trend change. Results: The 5-year relative survival rates of cancer were 41.92% to 53.65% from 2010 to 2016 for residents in Tianjin, with an increasing trend (t=4.81, P=0.005), and the average was 48.56%. The survival rate of females was higher than that of males (57.71%vs. 39.20%), and the survival rate of urban residents was higher than that of rural residents (49.38% vs. 47.24%). The 5-year relative survival rates were 63.14%, 78.39%, 58.25% and 32.67% in 0-14, 15-44, 45-64 and 65 and above age groups, respectively. The median relative survival times of all cancer were 2.34 to 6.00 years from 2010 to 2016 in Tianjin, with an increasing trend (t=3.86, P=0.012). The average of median relative survival times was 4.11 years. The median survival time of females was longer than that of males (11.99 years vs. 2.03 years), and the time of urban residents were longer than that of rural residents (4.60 years vs. 3.43 years). The median relative survival time were 12.07, 11.92 and 1.34 years in 15-44, 45-64 and 65 and above age groups, respectively. Conclusions: The cumulative survival rate of cancer increased significantly from 2010 to 2016 in Tianjin, indicating that the prevention and treatment effect of cancer is obvious. The focus should be on male, rural areas, higher age group, and targeted prevention and treatment measures should be taken to lung, esophagus, liver, gallbladder and pancreatic cancer.

[Clinical features and death risk factors of pneumocystis jirovecii pneumonia in kidney disease patients with immunosuppressive therapy].

To investigate the clinical features and death risk factors of pneumocystis jirovecii pneumonia (PJP) in kidney disease patients with immunosuppressive patients. A Retrospective case series study was performed in 52 PJP patients with kidney disease who received immunosuppressive therapy in Nephrology or Respiratory department of Peking University First Hospital from January 1, 2006 to August 31, 2021. Patients were divided into survival group (36 cases) and death group (16 cases) according to their clinical outcomes. Univariate analysis was performed to compare the differences of clinical features between the two groups. Multivariate logistic regression model was used to analyze the death risk factors. The results showed that the median serum creatinine was 192.5 (109.8, 293.7) µmol/L, and the incidence of acute kidney injury was 63.5% (33/52). Univariate analysis showed that age (t=1.197,P=0.030), C-reactive protein level (t=2.378,P=0.022), time from onset to diagnosis (χ2=6.62,P=0.010), PJP severity (χ2=5.482,P=0.019), complicated with septic shock (χ2=3.997,P=0.046), mechanical ventilation (χ2=11.755,P=0.001), and blood purification therapy (χ2=4.748,P=0.029) were statistically significant. There were no statistically significant differences between the two groups in gender, duration and dosage of hormone therapy before PJP onset, intravenous methylprednisolone pulse therapy, immunosuppressant use, and serum creatinine level before and after hospitalization for anti-PJP treatment (all P>0.05). Multivariate analysis showed that the time from onset to diagnosis of PJP was >10 days (OR=40.945, 95%CI: 1.738-451.214; P=0.021) and severe PJP (OR=25.502, 95%CI: 1.426-74.806; P=0.028) was an independent death risk factor for kidney disease complicated with PJP of immunosuppressive therapy. In conclusion, the time from onset to diagnosis of PJP and PJP severity are independent death risk factors in patients with kidney disease complicated with PJP of immunosuppressive therapy. Close attention should be paid to oxygenation condition and early diagnosis can prevent the aggravation of PJP and improve the prognosis.

[Liver cancer treatment with mitochondrial homeostasis].

Systemic treatment, including molecular targeted therapy, immunotherapy, and chemotherapy, is an important means of achieving long-term survival in patients with intermediate-and advanced-stage liver cancer. However, some patients are insensitive to treatment and even develop drug resistance. Mitochondria are the center of cellular energy metabolism and, at the same time, are the priority targets for systemic therapy. Mitochondrial homeostasis plays an important role in the treatment of liver cancer. The relationship between the two advances is elucidated so as to provide better ideas for the clinical treatment of liver cancer.

[Mechanisms by which Mettl3 regulates pericyte-myofibroblast transdifferentiation through PI3K/AKT signaling pathway].

Objective: To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis. Methods: C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×106 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson's trichrome to assess the extent of renal fibrosis. Results: Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×106 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group (P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group (P<0.05), but increased again upon addition of SC79. Conclusion: Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Evidence of a New Excited Charmed Baryon Decaying to Σ_{c}(2455)

We present the study of B[over ¯]^{0}→Σ_{c}(2455)^{0,++}π^{±}p[over ¯] decays based on 772×10^{6} BB[over ¯] events collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The Σ_{c}(2455)^{0,++} candidates are reconstructed via their decay to Λ_{c}^{+}π^{∓} and Λ_{c}^{+} decays to pK^{-}π^{+}, pK_{S}^{0}, and Λπ^{+} final states. The corresponding branching fractions are measured to be B(B[over ¯]^{0}→Σ_{c}(2455)^{0}π^{+}p[over ¯])=(1.09±0.06±0.07)×10^{-4} and B(B[over ¯]^{0}→Σ_{c}(2455)^{++}π^{-}p[over ¯])=(1.84±0.11±0.12)×10^{-4}, which are consistent with the world average values with improved precision. A new structure is found in the M_{Σ_{c}(2455)^{0,++}π^{±}} spectrum with a significance of 4.2σ including systematic uncertainty. The structure is possibly an excited Λ_{c}^{+} and is tentatively named Λ_{c}(2910)^{+}. Its mass and width are measured to be (2913.8±5.6±3.8) MeV/c^{2} and (51.8±20.0±18.8) MeV, respectively. The products of branching fractions for the Λ_{c}(2910)^{+} are measured to be B(B[over ¯]^{0}→Λ_{c}(2910)^{+}p[over ¯])×B(Λ_{c}(2910)^{+}→Σ_{c}(2455)^{0}π^{+})=(9.5±3.6±1.6)×10^{-6} and B(B[over ¯]^{0}→Λ_{c}(2910)^{+}p[over ¯])×B(Λ_{c}(2910)^{+}→Σ_{c}(2455)^{++}π^{-})=(1.24±0.35±0.10)×10^{-5}. Here, the first and second uncertainties are statistical and systematic, respectively.

[Research status and existing problems of lumbar pedicle double-trajectory screw technique].

Lumbar pedicle double-trajectory screw technique refers to the placement of traditional pedicle screw combined with cortical bone trajectory screw in the same pedicle, which has been proved to provide higher fixation strength in osteoporotic vertebral body fixation, and is also a less invasive surgical choice for revision of adjacent segment disease. At present, related basic research and clinical application exploration of double-trajectory screw technique have been carried out, but there are still many problems that need to be further investigated and clarified. The clinical application and existing problems of double screw technique were discussed in this paper for clinical reference.

[Clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae].

To explore the clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP), in order to provide reference for the prevention and treatment of CRKP infection. Retrospective analysis was performed on 510 clinical isolates of CRKP from January 2017 to December 2021, and strain identification and drug sensitivity tests were conducted by MALDI-TOF mass spectrometer and VITEK-2 Compact microbial drug sensitivity analyzer. The carbapenemase phenotype of CRKP strain was detected by carbapenemase inhibitor enhancement test. The CRKP strain was further categorized by immunochromogenic method and polymerase chain reaction (PCR) was used for gene detection. The results showed that 302 strains (59.2%) were derived from sputum, 127 strains (24.9%) from urine and 47 strains (9.2%) from blood. 231 (45.3%) were mainly distributed in intensive care, followed by 108 (21.2%) in respiratory medicine and 79 (15.5%) in neurosurgery. Drug susceptibility test result shows that the resistant rate of tigecycline increased from 1.0% in 2017 to 10.1% in 2021, the difference was statistically significant (χ2=14.444,P<0.05). The results of carbapenemase inhibitor enhancement test showed that 461 carbapenemase strains (90.4%) of 510 CRKP strains, including 450 serinase strains (88.2%), 9 metalloenzyme strains (1.8%), and 2 strains (0.4%) produced both serine and metalloenzyme. 49 strains (9.6%) did not produce enzymes. Further typing by immunochromogenic assay showed that 461 CRKP strains were KPC 450 (97.6%) and IMP 2 (0.4%). 7 NDM (1.5%); 2 strains of KPC+NDM (0.4%); PCR results were as follows: 450 strains of blaKPC (97.6%), 2 strains of blaIMP (0.4%), 7 strains of blaNDM (1.5%), and 2 strains of blaKPC+NDM (0.4%). In conclusion, CRKP strains mainly originated from sputum specimens and distributed in intensive care department, and the drug resistance characteristics were mainly KPC type in carbapenemase production. Clinical microbiology laboratory should strengthen the monitoring of CRKP strains, so as to provide reference for preventing CRKP infection and reducing the production of bacterial drug resistance.

[Analysis of clinical characteristics and treatment status of atopic dermatitis in a children's hospital in Beijing from 2015 to 2019].

To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ2=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ2=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.

[The distribution of blood pressure and associated factors of the elderly with type 2 diabetes in Jiangsu Province].

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m2, fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m2, male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.

[Research progress on the mechanism and response strategies of molecular targeted drug resistance in liver cancer].

Molecular targeted drugs are one of the treatments for hepatocellular carcinoma (HCC), the primary factor influencing their therapeutic efficacy is drug resistance. Diminished drug intake, greater efflux, improved DNA damage repair capacity, aberrant signal pathways, hypoxia, epithelial-mesenchymal cell transition, and the cellular autophagy system are summarized herein as aspects of the drug resistance mechanism. Simultaneously, effective strategies for addressing drug resistance are elaborated, providing ideas for better clinical treatment of HCC.

[Expression and protective effect of chemerin in idiopathic pulmonary fibrosis].

Objective: To explore the expression and the role of chemerin in idiopathic pulmonary fibrosis (IPF). Methods: Quantitative PCR and Western blotting were used to determine the mRNA and protein levels of chemerin in lung tissues from IPF patients and the controls. Clinical serum level of chemerin was analyzed by enzyme-linked immunosorbent assay. The mouse lung fibroblasts isolated and cultured in vitro were divided into the control, TGF-ß, TGF-ß+chemerin and chemerin groups. Immunofluorescence staining was used to observe the expression of α-smooth muscle actin (α-SMA). C57BL/6 mice were randomly divided into the control, bleomycin, bleomycin+chemerin, and chemerin groups. Masson and immunohistochemical staining were performed to evaluate the severity of pulmonary fibrosis. Expression of epithelial to mesenchymal transition (EMT) markers was detected by quantitative PCR and immunohistochemical staining in the in vitro and in vivo models of pulmonary fibrosis, respectively. Results: Compared with the control group, the expression of chemerin was downregulated in both the lung tissue and the serum of IPF patients. Immunofluorescence showed that treatment of fibroblasts with TGF-ß alone resulted in a robust expression of α-SMA, whereas treatment with TGF-ß and chemerin together exhibited the similar expression levels of α-SMA as the control group. Masson staining indicated that the bleomycin-induced pulmonary fibrosis model was constructed successfully, while treatment of chemerin partially alleviated the damage of lung tissue. Immunohistochemical staining showed that the expression of chemerin in the lung tissue was significantly decreased in the bleomycin group. Quantitative PCR and immunohistochemistry showed that chemerin attenuated EMT induced by TGF-ß and bleomycin both in vitro and in vivo. Conclusions: The expression of chemerin was reduced in patients with IPF. Chemerin may play a protective role in the development of IPF by regulating EMT, providing a new idea for the clinical treatment of IPF.

Search for a Light Higgs Boson in Single-Photon Decays of ϒ(1S) Using ϒ(2S)→π

We search for a light Higgs boson (A^{0}) decaying into a τ^{+}τ^{-} or µ^{+}µ^{-} pair in the radiative decays of ϒ(1S). The production of ϒ(1S) mesons is tagged by ϒ(2S)→π^{+}π^{-}ϒ(1S) transitions, using 158×10^{6} ϒ(2S) events accumulated with the Belle detector at the KEKB asymmetric energy electron-positron collider. No significant A^{0} signals in the mass range from the τ^{+}τ^{-} or µ^{+}µ^{-} threshold to 9.2 GeV/c^{2} are observed. We set the upper limits at 90% credibility level (C.L.) on the product branching fractions for ϒ(1S)→γA^{0} and A^{0}→τ^{+}τ^{-} varying from 3.8×10^{-6} to 1.5×10^{-4}. Our results represent an approximately twofold improvement on the current world best upper limits for the ϒ(1S)→γA^{0}(→τ^{+}τ^{-}) production. For A^{0}→µ^{+}µ^{-}, the upper limits on the product branching fractions for ϒ(1S)→γA^{0} and A^{0}→µ^{+}µ^{-} are at the same level as the world average limits, and vary from 3.1×10^{-7} to 1.6×10^{-5}. The upper limits at 90% credibility level on the Yukawa coupling f_{ϒ(1S)} and mixing angle sinθ_{A^{0}} are also given.

Controlled pilot test of a translated cardiac rehabilitation education curriculum in percutaneous coronary intervention patients in a middle-income country delivered using WeChat: acceptability, engagement, satisfaction and preliminary outcomes.

In China, despite the rapid increase in percutaneous coronary interventions (PCIs), cardiac rehabilitation (CR) is just burgeoning, leaving a need for comprehensive evidence-based education curricula. This pilot study assessed the acceptability of Simplified Chinese CR education delivered via booklets and videos on WeChat asynchronously and the impact on improving knowledge, risk factors, health behaviors and quality of life. In this pre-post, controlled, observational study, interested PCI patients received the 12-week intervention or usual care and WeChat without education. Participants completed validated surveys, including the Coronary Artery Disease Education-Questionnaire and Self-Management Scale. Acceptability (14 Likert-type items), engagement (minutes per week) and satisfaction were assessed in intervention participants. Ninety-six patients consented to participate (n = 49 intervention), of which 66 (68.8%) completed the follow-up assessments. Twenty-seven (77.1%) retained intervention participants engaged with the materials, rating content as highly acceptable (all means ≥4/5) and satisfactory (2.19 ± 0.48/3); those engaging more with the intervention were significantly more satisfied (P = 0.03). While participants in both groups achieved some improvements, only intervention participants had significant increases in disease-related knowledge, reductions in body mass index and triglycerides, as well as improvements in diet (all P < 0.05). In this first study validating the recently translated CR patient education intervention, acceptability and benefits have been supported.

[Pancreatic ß-cell dedifferentiation detected by flow cytometry].

Objective: To establish a method for detecting pancreatic ß-cell dedifferentiation using flow cytometry. Methods: Experimental study. Min6 (mouse ß cell line), αTC1-6 (mouse α cell line), HepG2 (human hepatocellular carcinoma cells) and mouse F9 cells (mouse teratocarcinoma cell) were cultured with conventional medium. Min6 cells were treated with interleukin-1ß (IL-1ß) in combined with tumor necrosis factor α (TNFα), or palmitic acid (PA) overnight and stained with anti-chromogranin A (ChgA), anti-insulin (Ins), anti-glucagon (Gcg), anti-SRY-box transcription factor 9 (Sox9) and anti-octamer binding transcription factor 4 (Oct4) antibodies, respectively. Flow cytometry was applied to detect the pression of ChgA, Ins, Gcg, Sox9, and Oct4 in the cells, respectively. Unpaired Student t test was used for statistical analysis. Results: Flow cytometry analyses showed that Ins and ChgA were highly expressed in Min6 cells, Gcg was highly expressed in αTC1-6, Sox9 was highly expressed in HepG2, and Oct4 was highly expressed in F9 cells, respectively (around 90%). Treatment of Min6 cells with IL-1ß+TNFα significantly decreased Ins positive staining cells (92.775%±1.702% vs. 97.125%±0.246%, P=0.045), while increased Sox9 positive staining cells (41.675%±0.390% vs. 25.875%±3.348%, P=0.003). No significant changes in ChgA and Oct4 expression could be viewed (both P>0.05). PA treatment elevated the number of Gcg positive staining cells (54.500%±3.597% vs. 41.160%±3.007%, P=0.022). The levels of mRNA expression by qPCR of the above proteins were in consistent with the levels of protein expression by flow cytometry in Min6 cells. Conclusion: Flow cytometry can be used to detect proteins expressed in dedifferentiated models of ß cells, which provides a new method for identify dedifferentiation of pancreatic ß cells.

[Associations between personal fine particulate matter and blood lipid profiles: A panel study in Chinese people aged 60-69 years].

Objective: To explore the association between short-term exposures to fine particulate matter (PM2.5) on blood lipids in the elderly. Methods: In this panel study, five repeated measurements were performed on 76 people aged 60-69 in Jinan city. Each participant had a PM2.5 monitor for 72 hours before each health examination, including a questionnaire survey, physical examination, and biological sample collection. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were examined, and non-HDL-C concentrations were calculated by subtracting HDL-C from TC. The generalized linear mixed-effects model was used to quantify the association of personal PM2.5 exposure at different lag with blood lipids and dyslipidemia. Results: The age of 70 participants was (65.0±2.8) years, of which 48.6% (34/70) were males. The BMI of participants was (25.0±2.5) kg/m2. Their TC, TG, LDL-C, HDL-C, and non-HDL-C concentrations were (5.75±1.32), (1.55±0.53), (3.27±0.94), (1.78±0.52), and (3.97±1.06) mmol/L, respectively. Generalized linear mixed-effects model showed that after adjusting for confounding factors, at lag 72 hours, each 10 µg/m3 increase in PM2.5 was associated with the percentage change in TC, LDL-C, HDL-C and non-HDL-C about 1.77% (95%CI: 1.22%-2.32%), 1.90% (95%CI: 1.18%-2.63%), 1.99% (95%CI: 1.37%-2.60%) and 1.74% (95%CI: 1.11%-2.37%), and the OR values (95%CI) of hypercholesterolemia, hypertriglyceridemia and hyperbetalipoproteinemia were 1.11 (1.01-1.22), 1.33 (1.03-1.71) and 1.15 (1.01-1.31), respectively. Conclusion: There is a significant association of short-term PM2.5 exposure with the concentration of blood lipids and the risk of dyslipidemia in the elderly.

[Advancement in endovascular therapy of aortoiliac occlusive disease].

Aortoiliac occlusive disease (AIOD) refers to the stenosis and occlusion of the distal abdominal aorta and(or) bifurcation of the aortoiliac artery,which is mainly caused by atherosclerosis,leading to pelvic and lower limb ischemia.Open surgery has always been the main treatment for complex AIOD.However,in recent years,with the development of endovascular surgery technologies and medical instruments,its treatment concept has been greatly changed.More and more clinical evidence has proved that the long-term efficacy of endovascular therapy is not inferior to that of traditional open surgery,so minimally invasive endovascular therapy has become the preferred treatment for AIOD.

[The prevention and therapy of corneal ulcers in patients with large-area thermal burns].

Objective: To evaluate the characteristics of ocular injury in patients with severe extensive thermal burns, and to explore the effective methods to prevent and treat corneal ulcers related to severe burns. Methods: A retrospective case series study. Between 2010 and 2019, Sixteen severe thermal burn patients with burn sizes>70% of the total body surface area involving the ocular region were admitted to the Burns and Plastic Surgery Division of Chinese PLA General Hospital, and consult with Ophthalmology Division. There were deep second-degree to fourth-degree burns in the eyelids. In the eleven surviving patients, 22 eyes presented ectropion. Eyelid full-thickness skin grafting (EFTSG) combined with or without tarsorrhaphy was performed in 20 eyes due to severe corneal exposure. Two eyes received partial blepharorrhaphy because of mild ectropion. The ocular manifestations and treatment outcomes were reviewed and assessed. Results: The majority of the patients were youth, and the average age was (36.8±10.4) years. The burn area was 84.0%±9.1% of the body surface area. Corneal ulcers secondary to lagophthalmos occurred at (35.1±15.6) days after burning in 75% (24/32) of eyes. Perforation was found in 18.8% (6/32) of eyes. Among the 22 operated eyes, the corneal ulcer was repaired in all 9 eyes receiving EFTSG with tarsorrhaphy, whereas ectropion recurred in 8 of 11 eyes only receiving EFTSG, and 4 eyes underwent further surgery due to corneal epithelial defects. Conclusions: In patients with severe large-area thermal burns, corneal ulcers are common complications. Prevention of corneal exposure is vital because the treatment of corneal ulceration is difficult due to eyelid deformity, inflammation and the absence of donor skin. Timely full-thickness skin grafting and blepharorrhaphy are effective approaches to preventing exposure keratopathy. To severe ulcers occur, conjunctival flap or Tenon's capsule covering combined with eyelid EFTSG and tarsorrhaphy is useful to rescue visual function.

Ecdysis triggering hormone is essential for larva-pupa-adult transformation in Leptinotarsa decemlineata.

In Drosophila melanogaster, ecdysis triggering hormone (ETH) is the key factor triggering ecdysis behaviour and promoting trachea clearance. However, whether ETH plays the dual roles in non-dipteran insects is unknown. In this survey, we found that Ldeth mRNA levels were positively correlated with circulating 20-hydroxyecdysone (20E) titers in Leptinotarsa decemlineata. Ingestion of an ecdysteroid agonist halofenozide or 20E stimulated the transcription of Ldeth, whereas RNA interference (RNAi) of ecdysteroidogenesis (LdPTTH or LdSHD) or 20E signalling (LdEcR, LdUSP or LdFTZ-F1) genes inhibited the expression, indicating ETH acts downstream of 20E. RNAi of Ldeth at the final instar stage impaired pupation. More than 80% of the Ldeth-depleted beetles remained as prepupae, completely wrapped in the old larval cuticles. These prepupae became withered, dried and darkened gradually, and finally died in soil. The remaining Ldeth hypomorphs pupated and emerged as abnormal adults, bearing smaller and wrinkle elytrum and hindwing. Moreover, the tracheae in the Ldeth hypomorphs were full of liquid. We accordingly proposed that the failure of trachea clearance disenabled air-swallowing after pupa-adult ecdysis and impacted wing expansion. Our results suggest that ETH plays the dual roles, initiation of ecdysis and motivation of trachea clearance, in a coleopteran.

Electron Acceleration during Macroscale Magnetic Reconnection.

The first self-consistent simulations of electron acceleration during magnetic reconnection in a macroscale system are presented. Consistent with solar flare observations, the spectra of energetic electrons take the form of power laws that extend more than two decades in energy. The drive mechanism for these nonthermal electrons is Fermi reflection in growing and merging magnetic flux ropes. A strong guide field suppresses the production of nonthermal electrons by weakening the Fermi drive mechanism. For a weak guide field the total energy content of nonthermal electrons dominates that of the hot thermal electrons even though their number density remains small. Our results are benchmarked with the hard x-ray, radio, and extreme ultraviolet observations of the X8.2-class solar flare on September 10, 2017.