Objective:To characterize the complete genome sequence and elucidate the structural features of norovirus (NoV) isolate SD20200267.Methods:The viral nucleic acid was extracted from patient samples, followed by amplification and sequencing for genotyping based on the nucleotide sequences. The metagenomic sequencing technology was utilized for whole genome sequencing, and subsequent analysis was performed on the acquired nucleotide sequences.Results:The complete genome sequence of the SD20200267 strain, spanning a total length of 7 465 nucleotides, was successfully obtained. The SD20200267 strain belongs to the GⅡ.12 and GⅡ.P16 genotypes in the VP1 and RdRp regions, respectively. The nucleotide sequence identity of SD20200267 strain with other GⅡ.12[P16] strains ranged from 96.0% to 97.3%, exhibiting 15 amino acid variations. The strain displayed evidence of recombination, with the recombination site located in the overlapping region of ORF1 and ORF2.Conclusions:SD20200267 is classified as a GⅡ.12[P16] strain, and recombination was observed in the overlapping region of ORF1 and ORF2.

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8⁺PD1⁺TCF1⁺ progenitor exhausted T cells (TCF1⁺Tex^prog) and CD8⁺PD1⁺TCF1^- terminally exhausted T cells (TCF1^-Tex^term). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1^-Tex^term represented a greater proportion of CD8⁺PD1⁺Tex than TCF1⁺Tex^prog in most patients. TCF1⁺Tex^prog produced abundant TNFα, while TCF1^-Tex^term expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1^-Tex^term exhibited a polyfunctional TNFα⁺GZMB⁺IFNγ⁺ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1^-Tex^term were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1^-Tex^term was the major CD8⁺PD1⁺Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1^-Tex^term was associated with greater Treg abundance.
CD8-Positive T-Lymphocytes ; Head and Neck Neoplasms/therapy* ; Humans ; Immunotherapy/methods* ; Prognosis ; Programmed Cell Death 1 Receptor ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha

Objective:To compare the efficacy and safety of Changsulin ? with Lantus ? in treating patients with type 2 diabetes mellitus (T2DM). Methods:This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin ? or Lantus ? treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results:After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin ? and in Lantus ?, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin ? and Lantus ? in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin ? and Lantus ?, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin ? and Lantus ?, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions:Changsulin ? shows similar efficacy and safety profiles compared with Lantus ? and Changsulin ? treatment was well tolerated in patients with T2DM.

Objective:To explore effective schemes for improving cognitive function in patients with subjective cognitive decline (SCD) by EEG neurofeedback (NF) technique.Methods:Ten SCD patients recruited in Department of Neurology, Xuanwu Hospital, Capital Medical University from April 2019 to August 2019, were chosen in our study; all patients were subjected to neuro-regulation of mismatched negativity (MMN) for 5 times in 2 weeks by EEG NF technique. By using the midlines of frontal zone (Fz), central zone (Cz) and peak zone (Pz) as training electrodes, auditory tones (1000 Hz as standard stimulus, individual hearing discrimination threshold as deviation stimulus) were used to induce MMN characteristics of event-related potential (ERP) via Oddball paradigm. SCD patients received visual disc stimulation feedback with dynamic neural signal activity. ERP waveforms and standard MMN characteristics (amplitude and latency) before and after training were used to evaluate the changes in neural activity of these patients; nine N-Back working memory tasks (three types×three gradients) and hearing discrimination ability tests were used in these patients to evaluate the improvement of cognitive competence.Results:ERP analysis showed that the MMN waveforms in SCD patients after training were obviously different as compared with those before training; their standard stimulus and deviant stimulus in the point-by-point paired t-test analysis were significant different ( P<0.05). The MMN amplitudes at the Fz, Cz and Pz electrodes in these patients after training were significantly higher than those before training ( P<0.05). The accuracy of auditory tone 3-Back task in SCD patients was statistically significant before and after training ( P<0.05). Conclusion:NF based on MMN can significantly improve the MMN amplitude and accuracy of auditory working memory task in patients with SCD, which might provide a potentially effective cognitive intervention method for patients with early AD and the elderly with normal memory decline.

Objective: To analyze the urinary iodine status of urban and rural residents in some areas of Gansu Province and its related influencing factors, and to provide certain references for scientific iodine intake of urban and rural residents in Gansu Province. Methods: Subjects in Gansu Province with normal thyroid function were recruited in the investigation of thyroid diseases and iodine nutritional status, conducted a questionnaire survey and measured height, weight, waist circumference, collected 1 urine sample, and tested their urinary iodine levels. The urinary iodine levels of different groups were compared based on different gender, region, age, body weight, the waist, and salt intaking. The affecting factors of urinary iodine levels were analyzed by multiple linear regression models. Results: Totally 1 964 subjects were recruited, including 1 099 males, and 865 females. The age was (41.23 ± 14.75) years old. The median urinary iodine of the selected group was 225.60 (158.80, 311.58) μg/L. The urinary iodine level of rural residents was significantly higher than that of urban residents [μg/L: 249.80 (180.58, 336.88) vs 206.25 (148.03, 280.33), Z=-8.015, P < 0.05], and there was no significant difference between the urinary iodine levels of male and female [μg/L: 222.40 (161.60, 298.90) vs 230.60 (158.00, 326.40), P > 0.05]. The composition ratio of < 100 μg/L group in rural areas was lower than that in urban areas (5.14% vs 8.27%, χ²= 7.45, P < 0.05), and the composition ratio of ≥300 μg/L group was higher than that in urban areas (34.93% vs 21.51%, χ²= 43.87, P < 0.05). The composition ratio of ≥300 μg/L group in male was lower than that in female (24.57% vs 31.21%, χ²= 10.73, P < 0.05). The multiple linear regression analysis showed that lived in rural areas, age, moderate and severe salt intaking, student, and weight were independently correlated with urinary iodine levels (β= 0.074, -0.001, 0.059, 0.034, 0.096, -0.003, P < 0.05). And the urinary iodine levels were decreased with age and weight increased (P < 0.05). Conclusions At present, the iodine nutrition level of urban and rural residents in some areas of Gansu Province is generally over the adequate level. The urinary iodine level of rural residents is higher than that of urban residents. In the future, we should pay attention to the impact of different living areas, salt intaking and body weight on urinary iodine levels to prevent thyroid diseases.

Ischemic stroke is one of the diseases that seriously threaten human health. It is characterized by the high morbidity, disability rate and mortality, and has been lacking effective treatment. Its occurrence is related to metabolic disorder, calcium overload, free radical injury, inflammatory reaction, etc. Gardeniae Fructus not only has antipyretic, analgesic, hepatoprotective and cholagogic effects, but also has protective effects against ischemic brain injury. At present, there are more studies about the main components of Gardeniae Fructus against ischemic brain injury, but the mechanism is unclear. In this paper, the mechanism of the main active ingredients from Gardeniae Fructus in the treatment of cerebral ischemia injury in recent years was reviewed, and the effective component monomer and the whole were analyzed, so as to provide a basis for the prevention and treatment of ischemic brain injury of Gardeniae Fructus decoction pieces, and provide a reference for further research and application of this decoction pieces.

Objective To investigate the expression of sialic acid-binding immunoglobulin-like-lectin-1 (Siglec-1)in the peripheral blood mononuclear cell (PBMC) of patients with autoimmune thyroiditis ( AIT) and its relationship with AIT. To explore the moduratory role of activated Siglec-1 on the differentiation of T cells and the promotion of in flammation after PBMC culture. Methods The peripheral whole blood and serum samples were collected from 30 AIT patients with normal thyroid function and 30 sex-and age-matched controls. The expression of sSiglec-1 in serum was detected by ELISA. The expression of Siglec-1 in PBMC was detected by RT-PCR and WB. The expression of Siglec-1 in CD14+ monocytes and the proportion of Th1 and Th17 cells in each group were detected by flow cytometry. The PBMC in AIT or control was stimulated with NaI in the presence or absence of LPS for 72 h. The expression of Siglec-1 in CD14+ monocytes and the proportion of Th1 and Th17 cells were detected by flow cytometry. Results sSiglec-1 in serum, Siglec-1 mRNA, and Siglec-1 protein in AIT patients'PBMC were higher than those in control group ( P＜0. 01). The expression of Siglec-1 in CD14+ monocytes by flow cytometry and differentiation of Th1 and Th17 cells were significantly higher than that in control group ( both P＜0. 01). The expression of Siglec-1 in control and AIT patients was up-regulated by 5×10-5 mmol/L to 1×10-2 mmol/L stimulated with NaI in the presence or absence of LPS for 72 h (P＜0.01), but the differentiation of Th1 and Th17 cells was up-regulated only in patients (P＜0.01), and in a dose-dependent manner. Conclusion Elevated Siglec-1 expression in PBMCs and monocytes can potentially serve as a biomarker for AIT. Iodine may affect Th1 and Th17 cell differentiation by activating Siglec-1 to adjust the AIT immune response.

Objective To evaluate the safety and efficacy of denosumab in treatment of patients with pelvic giant cell tumor of bone (GCTB) during perioperative period. Methods This is a retrospective observational study. Twenty-three patients diagnosed with pelvic GCTB undergoing perioperative denosumab treatment in Musculoskeletal Tumor Center of Peking University People's Hospital from January 2014 to December 2016 were reviewed. The subjective adverse reactions and mandibular X-ray films were used to assess the drug safety. As for efficacy, imaging findings (including X-ray, CT, magnetic resonance imaging) were reviewed. MSTS-93 scoring system was applied in the postoperative functional assessment. Histological response rate, objective response rate, clinical benefit rate and event-free survival rate were all used to deficit the efficacy of denosumab in the treatment of pelvic GCTB combined with surgery. All the results of postoperative were compared statistically with pelvic GCTB patients who underwent surgery in the same hospital from 1999 to 2009. Results All the patients were firstly diagnosed as classic GCTB except for one case which was malignant pelvic GCTB. All patients received denosumab preoperatively and/or postoperatively, and the average number of medications was 8.43. According to the surgical patterns, patients were divided into intralesional surgery group (13 cases) and wide resection group (10 cases). The follow-up was 5-47 months(mean:27.30 months),recurrence was observed in 2 cases in the intralesional surgery group, none in the wide resection group. After drug administration, 13 cases were partial response, 7 cases were stable disease, the objective response rate was 65.0 % (13/20), and the histologically clearance rate of giant cells was 85.0 % (17/20). No case of osteonecrosis of the jaw was observed in this study, and all laboratory indicators were normal. The average postoperative MSTS-93 score was 26.87. Compared with pelvic GCTB patients who underwent surgical treatment from 1999 to 2009, in the intralesional surgery group, there was no significant difference in the recurrence rate [15.4 % (2/13) vs. 30.8 % (4/13), P = 0.514], but the limb function was significantly increased (P= 0.002). Conclusions Denosumab combined with surgery plays an important role in the multidisciplinary treatment of pelvic GCTB. The neoadjuvant strategy can reduce patient's intraoperative blood loss by shrinking the tumor size which makes the intralesional curettage surgery possible, and also diminishing the recurrence rate. But more attention should be paid to secondary malignant GCTB during the use of denousmab.

Objective To investigate the effect of different serum sodium levels on heart function and prognosis in very elderly patients with heart failure. Methods Totally 152 elderly patients(aged ≥ 85 years)with hyponatremia were enrolled.Based on the serum sodium level ,they were divided into mild(125 mmol/L ≤ Na+ < 135 mmol/L) ,moderate(125 mmol/L ≤ Na+ < 135 mmol/L) ,and severe hyponatremia(Na+ < 115 mmol/L)groups ,and 76 patients with normal blood sodium level(Na+ ≥ 135 mmol/L)were selected as control group. The general data ,levels of serum creatinine and N-terminal pro-brain natriuretic peptide (NTproBNP)and prognosis were compared among the above groups. Results Compared with the control group ,patients with severe hyponatremia were much older ,with more diuretics administration ,higher level of serum creatinine , lowerlevelofeGFRandleftventricularejectionfractions[(38.1±3.9)％ vs.(45.2±9.7)％ ].There were higher incidences of coronary atherosclerotic heart disease [72.4％ (n=21)vs. 56.6％ (n=43)] ,diabetes[41.4％ (n=12)vs. 23.7％ (n=18)] ,chronic renal insufficiency [22.6％ (n=8)vs. 11.8％ (n=9)] ,stroke[20.6％ (n=6)vs. 9.2％ (n=7)]in patients with severe hyponatremia compared with other groups. The severe hyponatremia group showed significantly higher levels of NTproBNP [(4823. 9 ± 588. 1 )ng/L v s. (1124. 4 ± 349. 1 )ng/L ,(1836. 2 ± 369. 3 )ng/L ,(2894. 1 ± 687. 3 )ng/L ]and higher rates of mortality [27.6％ (n=8) vs.5.3％ (n=4) ,7.6％ (n=6) ,13.6％ (n=6)]as compared to the control group ,mild and moderate hyponatremia groups. Furthermore ,length of stay in hospital were markedly longer in patients with severe hyponatremia than those with mild and moderate hyponatremia[(11.1 ± 7.1)d vs. (19.6 ± 5.7)d ,(16.1 ± 4.2)d] . Conclusions Hyponatremia is a common type of electrolyte disorder in very elderly patients with heart failure ,and severe hyponatremia may predictand increased risk of death.

Objective To explore the relationship between ambient temperature variation and blood pressure fluctuations in acute ischemic stroke patients.Methods Clinical data of 5 730 ischemic stroke patients hospitalized at the Departments of Neurology and Geriatrics of The Second Hospital of Tianjin Medical University and air temperature data during the corresponding period were retrospectively analyzed.The relationship between air temperature and blood pressure in patients with acute ischemic stroke was analyzed.Results Of 5 730 patients,4 428 (77.28％)had hypertension and most of them were male(56.26％ 3 362 cases).The systolic and diastolic blood pressure levels were higher in hypertensive males than in hypertensive females[(153.9 ± 21.7) mmHg vs.(150.7 ± 23.6)mmHg,(85.9±13.3)mmHg vs.(83.0±12.5)mmHg,1 mm Hg=0.133 kPa,both P＜0.05].The systolic pressure tended to increase and diastolic pressure tended to decrease with increasing age (both P ＜ 0.05).The systolic and diastolic blood pressure levels of patients were slightly higher in autumn and winter than in spring and summer (P ＜ 0.05).The mean monthly maximum and minimum temperature had negative correlations with the systolic blood pressure of patients.There was a linear positive correlation between the average monthly diurnal temperature range and the systolic and diastolic blood pressure.The systolic or diastolic blood pressure increased by 0.088 mmHg or 0.076 mmHg respectively with each 1 ℃ drop in the mean monthly maximum and minimum temperature.The systolic or diastolic blood pressure increased by 1.043 mmHg or 0.654 mmHg respectively with each 1 ℃ increase in the average monthly diurnal temperature range.Conclusions Hypertension is a risk factor for ischemic stroke,and ambient temperature variation is related to baseline blood pressure fluctuations in hypertensive patients with acute ischemic stroke.The temperature reduction and the increase of average diurnal temperature rang can lead to the elevation of blood pressure,which is more obvious in autumn and winter,especially in elderly patients.