[Effects of high-fat and low-carbohydrate diet combined with radiotherapy on tumor microenvironment of Lewis lung cancer bearing mice].

Objective: To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts. Methods: C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry. Results: On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant (P＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant (P＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8+ T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞0.05]. The proportion, of CD4+ T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞0.05). Conclusion: High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.

[Molecular characteristics of ciprofloxacin-cefotaxime-azithromycin co-resistant Salmonella enterica Serovar Thompson in foodborne diseases in Hunan Province].

Objective: To investigate the molecular characteristics of ciprofloxacin-cefotaxime-azithromycin co-resistant Salmonella enterica serovar Thompson (S. Thompson) isolates from sporadic cases of foodborne diseases and aquatic foods in Hunan province. Methods: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates were selected from samples, and broth microdilution method was used to determine the resistance to 11 antibiotics of these isolates in vitro. Whole genome sequencing was used for investigating antimicrobial resistance gene patterns and phylogenetic relationships of strains. Results: Nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates were recovered from 19 S. Thompson isolates. Among nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates, eight of them harbored IncC plasmids, simultaneously carrying plasmid-mediated quinolone resistance (PMQR) genes qepA and qnrS1, ß-lactamase resistance gene blaCMY-2, azithromycin resistance gene mph(A), and one isolate harbored IncR plasmid, and carried PMQR genes qnrB4 and aac(6')-Ib-cr, blaOXA-10 and mph(A). Genetic environment analysis showed that qnrS1, qepA, mph(A) and blaCMY-2 genes might be integrated on genomes of strains by ISKra4, IS91, IS6100 and ISEcp1, respectively. Phylogenetic core genome comparisons demonstrated that ciprofloxacin-cefotaxime-azithromycin co-resistant isolates from patients and aquatic foods were genetically similar and clustered together. Conclusion: Ciprofloxacin-cefotaxime-azithromycin co-resistant S. Thompson isolates have been isolated from both human and aquatic food samples, suggesting that the spread of multidrug resistant Salmonella between human and aquatic animals.

[Clinical characteristics and whole exome sequencing results of patients with Möbius syndrome].

Objective: To analyze the clinical characteristics of patients with Möbius syndrome (MBS) and to explore likely pathogenic genes. Methods: Cross-sectional study. The study enrolled 18 sporadic MBS patients who visited the Eye Center of Beijing Tongren Hospital Affiliated to Capital Medical University from July 2018 to December 2021. All patients completed the general information questionnaire and underwent detailed ophthalmic examinations and general physical examinations. Seventeen patients received MRI examination of cranial nerves and the orbit. The peripheral venous blood of all patients and their nuclear family members was collected, the genomic DNA was extracted, and the pathogenic gene variations that may lead to MBS were identified by whole exome sequencing and bioinformatics analysis. Results: Among the 18 patients, there were 8 males and 10 females, and the age was (4.5±4.0) years (range, 8 months to 17 years). All patients showed congenital, bilateral or unilateral abduction deficit and facial weakness, which met the minimum diagnostic criteria of MBS. Among them, bilateral abduction deficit (16/18) and bilateral facial weakness (15/18) were more common. Nine patients were orthotopic in primary position, eight presented with esotropia, and one showed hypotropia. All patients had ametropia, of which 4 patients were diagnosed as amblyopia. Fifteen patients were also accompanied by other multiple congenital malformations, mainly characterized by abnormal development of glossopharynx (14/18) and limbs (5/18), and 7 patients were also accompanied by motor retardation. In addition, 9 patients had intrauterine exposure to adverse factors. Among the 17 patients who underwent MRI, 15 patients had bilateral hypoplasia of the abducens nerve, two had unilateral hypoplasia of the abducens nerve, 14 showed bilateral hypoplasia of the facial nerve, and three showed hypoplasia of the left facial nerve. Besides, some patients were also accompanied by hypoplasia of other cranial nerves, mainly the glossopharyngeal nerve and the hypoglossal nerve. No definite pathogenic variations were found by whole exome sequencing and bioinformatics analysis. Conclusions: The main clinical features of MBS were congenital abduction deficit and facial weakness, with complicated manifestations and variable severity. MRI showed absence or thinning of the abducens nerve and the facial nerve. The results of MRI can be used as a supplement to the diagnostic criteria of MBS. The mutation detection rate of MBS was low, and half of patients had exposure to adverse factors during pregnancy, suggesting that there was a multifactorial pathogenic mechanism in MBS.

First Detection of sub-PeV Diffuse Gamma Rays from the Galactic Disk: Evidence for Ubiquitous Galactic Cosmic Rays beyond PeV Energies.

We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.

Gamma-Ray Observation of the Cygnus Region in the 100-TeV Energy Region.

We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.

[Diagnostic performance of a novel Mycobacterium Tuberculosis specific T-Cell based assay for tuberculosis].

Objective: To evaluate the diagnosic performance of a novel Mycobacterium tuberculosis (MTB) specific T-cell based assay for tuberculosis, which targets the mRNA detection of interferon gamma-induced protein 10 (IP-10). Methods: Suspected tuberculosis patients were prospectively and consecutively recruited in Beijing Chest Hospital between March 2018 and November 2019, and individuals with lower risk of MTB infection were also recruited. IP-10.TB and T-SPOT.TB assays were simulataneously performed on peripheral blood samples. The diagnostic performance of IP-10.TB and T-SPOT.TB were analyzed using the receiver operating characteristic curve. Accordance of IP-10.TB and T-SPOT.TB was analyzed by Cohen's kappa test, while the correlation between the expression level of IP-10 mRNA in IP-10.TB test and the number of SFCs in T-SPOT.TB test were analyzed by Pearson correlation test. Results: A total of 235 patients with tuberculosis, 110 patients with other diseases and 153 individuals with lower risk of MTB infection were included in the final analysis. No significant difference was detected in the rate of indeterminate results between IP-10.TB assay (3/498, 0.60%) and T-SPOT.TB assay (6/498, 1.21%). The total sensitivity and specificity of IP-10.TB assay were 91.3% (95%CI 86.8%-94.6%) and 81.1% (95%CI 75.8%-85.7%). The specificity of IP-10.TB in individuals with lower risk of MTB infection was 98.0% (95%CI 94.4%-99.6%). The total sensitivity and specificity of T-SPOT.TB assay were 93.0% (95%CI 88.9%-96.0%) and 83.8% (95%CI 78.7%-88.1%). The specificity of T-SPOT.TB in individuals with lower risk of MTB infection was 100% (95%CI 97.6%-100.0%). No significant differences were detected in sensitivity and specificity between IP-10.TB and T-SPOT.TB assays (P>0.05). The positive coincidence rate of these 2 methods was 91.0% (95%CI 87.5%-94.5%), and the negative coincidence rate was 88.9% (95%CI 84.9%-92.9%) and the total coincidence rate was 90.0% (95%CI 87.3%-92.6%). The Cohen's kappa value was 0.80 (95%CI 0.75-0.85, P<0.001) between IP-10.TB and T-SPOT.TB assays. Conclusion: These results showed that the diagnostic performance of IP-10.TB was consistent with that in T-SPOT.TB, and this test could be a novel adjunctive tool for the diagnosis of tuberculosis.

[Analysis of factors influencing the remodeling of abdominal false lumen after thoracic aortic endovascular repair].

Objective: To examine the factors influencing the false lumen remodeling of abdominal aortic segment in the midterm and longterm after thoracic endovascular aortic repair (TEVAR). Methods: The data of patients with type B aortic dissection diagnosed and underwent TEVAR at the Department of Vascular and Endovascular Surgery, the First Medical Center, People's Liberation Army General Hospital, from November 2009 to November 2019 were analyzed retrospectively. Patients of acute or subacute long segment dissection with residual tears of abdominal but no thoracic segment and follow-up for more than one year were enrolled. Patients with operation-related complications, and dissection caused by trauma and Marfan syndrome were excluded. A total of 51 patients were enrolled, including 45 males and 6 females, with an age of (49.4±10.6) years (range: 31 to 72 years). The patients included in the analysis were divided into stable and enlarged group. The criteria for inclusion in the enlarged group were any of the following: (1) the maximum growth rate of the abdominal segment false lumen was ≥3 mm/year; (2) the maximum diameter of the abdominal aorta was ≥50 mm; (3) the diameter of the abdominal segment false lumen increased more than 10 mm. χ2 test, t-test and nonparametric test were used for univariate analysis. The variables with P≤0.1 were included in the Logistic multivariate stepwise regression to analyze the independent correlation factors, and the receiver operating characteristic (ROC) curve was used to calculate the cut-off value of the quantitative data. Results: All patients were divided into stable group (n=30) and enlarged group (n=21). The follow-up time of all patients was 42(29) months (range: 12 to 115 months). There were no significant differences in baseline characteristics, endovascular treatment characteristics and postoperative medication between the two groups (P>0.05). Compared with stable group,the number of residual tears around visceral arteries was more (2(1) vs. 1(1), Z=-2.829, P=0.005) and the number of lumbar arteries originating from false lumen was more (5(6) vs. 3(5), Z=-2.025, P=0.043) early after TEVAR in enlarged group. The number of residual tears around visceral arteries (OR=3.966, 95%CI: 1.552 to 10.131, P=0.004) was found to be the independent influence factor for the poor remodeling of the abdominal false lumen in multivariate Logistic regression analysis. ROC curve analysis showed that the cut-off value of the number of residual tears around visceral arteries was 2 at least (area under curve: 0.718). Conclusion: The incidence of poor remodeling of the abdominal false lumen after TEVAR was high. The number of residual tears around visceral arteries (≥2) could be independent influence factor to predict the poor remodeling of abdominal false lumen, and the follow-up of such patients should be strengthened in clinic.

[Evidence-based progress for the risk events of paclitaxel devices in treatment of peripheral artery disease].

With the development of endovascular technology for peripheral arterial diseases, paclitaxel drug-eluting stents and drug-coated balloons have been widely used in recent years. It has been proved that paclitaxel-coated devices have good clinical effects in reducing vascular restenosis. However, the clinical safety of paclitaxel devices has encountered challenges, some of the studies have shown that paclitaxel-coated devices may increase long-term mortality. In addition, some studies have confirmed the effectiveness and safety of paclitaxel devices, leading to this topic becoming the focus and hot spot of global attention. Whether paclitaxel-coated devices increase the risk of long-term death, whether paclitaxel doses are related to mortality, and the pharmacokinetics of paclitaxel devices should be examined.

[Research progress of the role of iodide transporters and its regulatory signal pathways in carcinomas].

Iodine transporters of basement membrane of thyroid follicular epithelial cells can participate and exchange the iodine ions across intracellular and extracellular. Among all of the iodine rich organs, iodine ions which only exist in colloidal of thyroid follicular epithelial cells can be functioned as the raw materials, which after oxidation, iodization and coupling, to synthesize thyroid hormone (TH) and to exert its biological functions. Therefore, the iodine transported function of iodide transporters plays a pivotal role for TH biosynthesis. Furthermore, functional studies show that the abnormal expression or dysfunction of iodide transporters might serves as tumor promoters or inhibitors via regulated the mTOR signal pathway, the MAPKs signal pathway, and the NF-κB signal pathway, together contributed to the regulation of cell proliferation, invasion, metastasis and apoptosis, in which plays the role of non iodide transported function. Therefore, the non iodine transported function of iodide transporters may plays the crucial role of tumor occurrence and progression of carcinoma. Based on this information, present study was devoted to systematic summarize the iodine transported function and non iodine transported function (may affects occurrence and progression of carcinoma) of the classical iodide transporters [sodium iodide symporter (NIS) and pendrin] and novel iodine transporters[ (cystic fibrosis transmembrane conductance regulator (CFTR) , sodium multivitamin transporter (SMVT) , and anoctamin 1 (ANO1) ], respectively, in order to provide a theoretical basis and literature review reference for underlying the mechanism of iodine transporters and its regulated signal pathways for the occurrence and progression of carcinomas.

Methods and clinical outcomes of in situ fenestration for aortic arch revascularization during thoracic endovascular aortic repair.

OBJECTIVE: Despite endovascular advances in fenestrated and branched devices, thoracic endovascular aortic repair (TEVAR) for arch pathologies remains challenging. The aim of this study was to provide a contemporary review on the current evidence for in situ fenestration during TEVAR and to evaluate its short- and mid-term clinical outcome in the management of arch pathology. METHODS: A systematic literature review on in situ fenestration of thoracic aortic stent-graft from January 2003 to September 2018 was performed under the instruction of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. RESULTS: Our initial search yielded 169 studies, of which 21 articles were relevant to the topic and were finally included. One hundred and forty-five in situ fenestration procedures in 99 patients were reviewed, involving 25 innominate arteries (17%), 33 left common carotid arteries (23%) and 87 left subclavian arteries (60%). Twelve patients (12/99, 12%) had two-vessel fenestration and three-vessel fenestration was performed in 17 patients (17/99, 17%). Technical success was achieved in 136 arteries (136/145, 93%). Talent/Valiant with monofilament twill woven polyester fabric was the most common (50/99, 51%) stent-graft used for fenestration. Three methods reported for in situ fenestration were needle, laser and radiofrequency. Needle was the most frequently used device for fenestration, which was performed in 60 patients (60/99, 61%). Three patients (3/99, 3%) died with 30 days, none were in situ fenestration TEVAR procedure-related. Perioperative complications including one (1%) retrograde type A aortic dissection, two (2%) type II endoleaks, and three (3%) strokes were reported. The pooled estimate for overall technical success, perioperative mortality and stroke was 88.3% (95% CI, 78.6%-93.9%), 5.9% (95% CI, 2.5%-13.4%) and 9.5% (95% CI, 4.1%-20.6%), respectively. Four patients (4/96, 4%) died during follow-up, none were aortic-related. All the fenestration bridging stents were reportedly patent, with only 1 (1/96, 1%) asymptomatic left subclavian stent stenosis. Two patients (2/96, 2%) with type II endoleak from left subclavian artery required secondary intervention. CONCLUSION: In situ fenestration appeared to be a feasible and effective method to extend proximal landing zone during TEVAR. It had an acceptable short-term result with high technical success and low fenestration related morbidity. Long-term durability data were lacking, and there was no high level evidence to recommend the routine use of in situ fenestration TEVAR for the management of arch pathology.

[Molecular epidemiology of Listeria monocytogenes isolated from ready-to-eat food in 2017 in China].

Objective: To analyze the molecular characteristics of Listeria monocytogenes strains from ready-to eat food in China. Methods: A total of 239 Listeria monocytogenes strains isolated from ready-to-eat food in 2017, all strains underwent whole-genome sequencing (WGS) , and comparisons uncovered population structure derived from lineages, clonal complex, serogroups, antimicrobial susceptibility and virulence, which were inferred in silico from the WGS data. Core genome multilocus sequence typing was used to subtype isolates. Results: All strains were categorized into three different lineages, lineage Ⅱ was the predominant types in food, and IIa was the main serogroups. CC8, CC101 and CC87 were the first three prevalent CCs among 23 detected CCs, accounting for 49.4%. Only 4.6% (11 isolates) of tested strains harbored antibiotic resistance genes, which were mostly trimethoprim genes (7 isolates, 2.9%). All strains were positive for LIPI-1, and only a part of strains harbored LIPI-3 and LIPI-4, accounting for 13.8% (33 isolates) and 14.2% (34 isolates), respectively. ST619 carried both LIPI-3 and LIPI-4. 51.5% (123 isolates) of strains carried SSI-1, and all CC121 strains harbored SSI-2. Different lineages, serogroups and CCs can be separated obviously through cgMLST analysis, and 24 sublineages were highly concordant with CCs. Conclusion: Ⅱa was the main serogroups in ready-to-eat food isolates in China; CC8, CC101 and CC87 were the prevalent CCs, and CC87 isolates was hypervirulent isolates, cgMLST method can be adopted for prospective foodborne disease surveillance and outbreaks detection.

[Influence of deformation of femoropopliteal artery on choice of stents].

In recent years, stent implantation has played an important role in solving femoropopliteal artery disease. Because part of the femoropopliteal artery is at the level of the knee joint, the deformation of this segment of the artery is greater when the lower limbs are bent, and the stent fracture rate is higher. Studies have showed that the deformation of the femoropopliteal artery mainly includes bending, twisting, axial compression and radial compression. The selection of stents with mechanical properties suitable for the deformation of artery in different sections can reduce the risk of fracture. The commonly used clinical stent designs (classic laser engraving stent, braided stent and covered stent) have large differences in mechanical properties. Braided stents with higher radial support are more suitable for treating popliteal artery disease, while covered stent has good compliance and can be used in all segments. Of course, the existing types of stents cannot meet all mechanical requirements. The design of the new stent needs to be studied, and its clinical results need to be confirmed by research.

First Detection of Photons with Energy beyond 100 TeV from an Astrophysical Source.

We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100 TeV. As a result, we observed 24 photonlike events with E>100 TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100 TeV from an astrophysical source.

[Application of MRI in the etiological diagnosis of special forms of strabismus].

Objective: To explore the imaging features of patients with special forms of strabismus and summarize the subtypes by using MRI imaging techniques. Methods: A retrospective case series study. Among the patients who visited the Beijing Tongren Hospital between 2006 and 2016, 1 113 patients were identified with special forms of strabismus after complete ophthalmic and orthoptic evaluations. These patients were further evaluated using several types of high-resolution MRI techniques of the oculomotor nerves in the brain, the cavernous sinus, and the orbits. Results: Among the 1 113 patients, 818 patients (73.5%) were identified with MRI abnormal conditions, and 295 patients (26.5%) were identified with MRI normal conditions. Nine different disease types were identified in the studied populations, which included 257 patients (23.1%) with congenital cranial dysinnervation disorders, 209 patients (18.8%) with thyroid associated ophthalmopathy, and 169 patients (15.2%) with abnormalities of the extraocular muscles. Other diseases included orbital fractures (3.3%, 37 patients), intraorbital inflammations (2.7%, 30 patients), tumors (2.3%, 26 patients), injuries of medial rectus muscle after endoscopic sinus surgery (1.2%,13 patients), and lesions of cavernous sinus (2.0%, 22 patients). Additional 55 patients (4.9%) were identified with other causes such as high myopia fixed esotropia, and so on. Conclusion: Summarizing the common clinical characteristics and rules with the help of MRI can further clarify the etiology of special forms of strabismus, and accurately guide the diagnosis and treatment of strabismus. (Chin J Ophthalmol, 2019, 55: 361-368).

Evaluation of the Interplanetary Magnetic Field Strength Using the Cosmic-Ray Shadow of the Sun.

We analyze the Sun's shadow observed with the Tibet-III air shower array and find that the shadow's center deviates northward (southward) from the optical solar disk center in the "away" ("toward") interplanetary magnetic field (IMF) sector. By comparing with numerical simulations based on the solar magnetic field model, we find that the average IMF strength in the away (toward) sector is 1.54±0.21_{stat}±0.20_{syst} (1.62±0.15_{stat}±0.22_{syst}) times larger than the model prediction. These demonstrate that the observed Sun's shadow is a useful tool for the quantitative evaluation of the average solar magnetic field.

[Efficacy and safety of Entecavir monotherapy switched from Lamivudine combined Adefovir Dipivoxil for chronic hepatitis B virus-related compensated liver cirrhosis].

Objective: To observe the efficacy and safety of de novo combination of Lamivudine(LAM) and Adefovir Dipivoxil (ADV) therapy counter to Entecavir (ETV) monotherapy in patients with chronic hepatitis B (CHB)- related compensated liver cirrhosis. Methods: Patients with chronic hepatitis B-related compensated cirrhosis who were initially treated with LAM and ADV for more than 1 year were randomly assigned to two groups, one half replaced with ETV monotherapy, and the other half continued LAM and ADV co-therapy. Liver biochemistry, renal biochemistry, estimated glomerular filtration rate, alpha-fetoprotein, HBV serology markers and serum HBV DNA were measured every 3 months. Urine ß2-microglobulin was measured every 6 months And retinol binding protein, followed up for 3 years. The mean values of the two groups were compared with t-test, and the rate of comparison was analyzed by x2 test. Results: A total of 580 cases were collected, 290 cases were replaced with ETV monotherapy, the other 290 patients continued to LAM and ADV combination therapy. In the ETV group, the rates of HBV DNA negative conversion at 1 year, 2 years and 3 years were 77.6%, 84.5% and 94.5% respectively, while the HBV DNA negative conversion rates at 1, 2 and 3 years in the LAM and ADV combination groups were 69.3%, 73.4% and 80.3% respectively. Among them, the negative rates of HBV DNA in the second year and the third year were P < 0.05, the difference was statistically significant. The 3-year cumulative gene-resistant rate in the ETV group was 1.4%, while the combined treatment was as high as 8.6%, and the difference was statistically significant in the two groups. The estimated value of serum creatinine and glomerular filtration rate in ETV group was followed by 3 years, and the baseline level was maintained, in the same group, the serum creatinine was higher than baseline, and the estimated value of glomerular filtration rate decreased. The results showed that there were 6.2%, 12.1%, 22.1% and 0, 0.3%, 1%, respectively, in 1, 2 and 3 years for the group of consecutive treatment and the replacement of ETV Group. The estimated glomerular filtration rate decreased by more than 30% compared with the baseline. The difference was statistically significant; the proportion of serum creatinine in the 1 year, 2 years and 3 years of the combined treatment group was 1.7%, 4.5% and 6.6%, compared with the baseline rise of > 50 µmol/l, and the ETV group was replaced in the 1 year, The values of 2 and 3 years were 0,0,0.7%, of which the 2nd and 3rd years were statistically significant; the proportion of microalbuminuria and retinol-binding protein in patients with combined treatment group was also significantly higher than that of Β2-m ETV Group. Conclusion: The initial combination of LAM and ADV therapy is inferior in terms of ETV monotherapy. Single therapy with ETV increase the rate of viral response, reduce the incidence of drug resistance, and also reduce the incidence of renal impairment in patients with chronic hepatitis B -related compensated liver cirrhosis.

CD137 is a Useful Marker for Identifying CD4+ T Cell Responses to Mycobacterium tuberculosis.

Upregulation of CD137 on recently activated CD8+ T cells has been used to identify rare viral and tumour antigen-specific T cells from the peripheral blood. We aimed to evaluate the accuracy of CD137 for identifying Mycobacterium tuberculosis (Mtb)-reactive CD4+ T cells in the peripheral blood of infected individuals by flow cytometry and to investigate the characteristics of these CD137+ CD4+ T cells. We initially enrolled 31 active tuberculosis (TB) patients, 31 individuals with latent TB infection (LTBI) and 25 healthy donors. The intracellular CD137 and interferon-γ (IFN-γ) production by CD4+ T cells was simultaneously detected under unstimulated and CFP10-stimulated (culture filtrate protein 10, a Mtb-specific antigen) conditions. In unstimulated CD4+ T cells, we found that the CD137 expression in the TB group was significantly higher than that in the LTBI group. Stimulation with CFP10 largely increased the CD4+ T cell CD137 expression in both the TB and LTBI groups. After CFP10 stimulation, the frequency of CD137+ CD4+ T cells was higher than that of IFN-γ+ CD4+ T cells in both the TB and LTBI groups. Most of the CFP10-activated IFN-γ-secreting cells were CD137-positive, but only a small fraction of the CD137-positive cells expressed IFN-γ. An additional 20 patients with TB were enrolled to characterize the CD45RO+ CCR7+ , CD45RO+ CCR7- and CD45RO- subsets in the CD137+ CD4+ T cell populations. The Mtb-specific CD137+ CD4+ T cells were mainly identified as having an effector memory phenotype. In conclusion, CD137 is a useful marker that can be used for identifying Mtb-reactive CD4+ T cells by flow cytometry.

[Changes and differences of DNA methylation in human macrophages infected with virulent and avirulent Mycobacterium tuberculosis].

Objective: To profile DNA methylation and compare differentially methylated region (DMR) of macrophages infected with virulent and avirulent strains of Mycobacterium tuberculosis (MTB). Methods: PMA(50 ng/ml) treated THP-1 macrophages were left uninfected or infected with the virulent H37Rv(THP-1/Rv) or avirulent H37Ra(THP-1/Ra). The genomic DNA was then extracted and DNA methylation was profiled via Reduced Representation Bisulfite Sequencing (RRBS). The DNA methylation pattern and DMRs between the tested samples were indentified. DMRs-associated genes were annotated, clustered by Gene Ontology (GO), and the pathways analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). mRNA expression of several DMR-associated genes were verified by Q-PCR, and Student's t-test was used to analyze the differential expression between either 2 samples. Results: The mostly DNA methylated C in 3 samples was in CG, accounting for 98% of all types of methylated C(CG, CGH, CHH). Besides, the average DNA methylation level in THP-1/Rv, THP-1/Ra and THP-1/NC were 7.72%, 7.38% and 7.58% in the promoter, and 9.90%, 9.57% and 9.80% in the CpG island (CGI), respectively. We identified 58 DMRs between H37Rv and H37Ra infected THP-1 macrophages with an average length of 152 bp. Six DMRs-associated genes were enriched. Among them, AP-1 and DDIT4 were differentially expressed in cells infected with H37Rv and H37Ra. Conclusions: Infection with MTB is not correlated with a large-scale gain or loss in DNA methylation in host cells. AP-1 and DDIT4 might be novel virulence-related genes regulated by DNA methylation of their corresponding promoter regions.

Association between transcription factor 7-like 2 genetic polymorphisms and development of type 2 diabetes in a Chinese population.

We conducted a hospital-based case-control study to evaluate the relationship between the transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism and type 2 diabetes mellitus risk in a Chinese population. Genotyping of TCF7L2 rs7903146 was carried out using the polymerase chain reaction-restriction fragment length polymorphism method. A chi-square test revealed a statistically significant difference between the distributions of rs7903146 genotypes in type 2 diabetes mellitus patient and control groups (chi-square = 10.49, P = 0.005). Using unconditional logistic regression analysis, we observed that the TT genotype of this polymorphism was significantly correlated with increased risk of developing type 2 diabetes mellitus compared to the CC genotype [odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.33-4.04]. Furthermore, we found that the rs7903146 sequence variation was also significantly associated with susceptibility to this disease under dominant (OR = 1.58, 95%CI = 1.09-2.28) and recessive models  (OR = 2.11, 95%CI = 1.25-3.62). We conclude that the TCF7L2 rs7903146 genetic polymorphism is independently associated with the risk of developing type 2 diabetes mellitus under co-dominant, dominant, and recessive models.

[Novel biomarkers for latent tuberculosis infection by plasma proteomic profiling].

OBJECTIVE: To screen specific biomarkers for latent tuberculosis infection by comparing the plasma proteomic profiling between latent tuberculosis infection and healthy controls. METHODS: The plasma proteins from 15 cases with latent tuberculosis infection and 15 healthy controls were detected by the label-free quantitative proteomic technology. Differential expressed proteins were analyzed by GO, KEGG, and BiNGO analysis. Student's t test was used to analyze the differential expression between 2 groups. RESULTS: Twenty-three candidate proteins were identified, among which 15 proteins were downregulated (<0.5-fold at P<0.05) and 8 proteins were upregulated (>2.0-fold at P<0.05) in the latent tuberculosis infection group. Bioinformatic analysis revealed 3 proteins AAT, C3 and C4A to be the most significant. CONCLUSION: There were differential plasma protein profiles between latent tuberculosis infection and healthy controls. Candidate proteins AAT, C3 and C4A were promising biomarkers for discriminating cases with latent tuberculosis infection from healthy persons.