Objective:To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes.Methods:A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality.Results:During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95 %CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status ( HR=1.97,95 %CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders ( HR=1.22, 95 %CI 1.08-1.39, P=0.002). Conclusions:Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.

Objective:To investigate the long-term effects of metabolically healthy obesity on the risks of type 2 diabetes, cardiovascular disease events, and its mortality over a 23-year follow-up.Methods:Based on the results of an oral glucose tolerance test, there were 519 participants with normal glucose tolerance and 630 with newly diagnosed type 2 diabetes enrolled in 1986 and then given to assess the long-term clinical outcomes during the 23-year follow-up in Daqing. Metabolically healthy obesity was defined as the overweight and obese individuals with no metabolic abnormalities (diabetes, hypertension, hyperlipidemia). Finally, we identified 682 participants (350 with normal glucose tolerance and 332 with newly diagnosed diabetes). They were divided into five groups: 211 individuals with metabolically healthy normal weight (MHNW group), 58 with metabolically healthy overweight and obesity (MHO group), 81, 109, 223 were metabolically unhealthy overweight and obesity with hypertension (MUHO group), type 2 diabetes (MUDO group), hypertension and diabetes (MUHDO group). Incidences of type 2 diabetes, morbidity and mortality of cardiovascular disease were compared among these groups.Results:Over 23 years, instead of the morbidity and mortality of cardiovascular disease, the incidence of type 2 diabetes in MHO group was two times higher than in MHNW group ( 24.1%, 12.5/1 000 person years vs 10.9%, 5.2/1 000 person years, P=0.01), with an age, sex, and smoking history-adjusted hazard ratio ( HR) of 2.42 (95% CI 1.24-4.74, P=0.01). The morbidity and mortality of cardiovascular disease in the groups of overweight and obesity with metabolically unhealthy were higher than in MHNW group, and increased across the subjects with MUHO, MUDO, MUHDO ( P<0.05). Conclusion:Compared with metabolically healthy normal weight participants, the metabolically healthy obese group was at increased risk of type 2 diabetes but not cardiovascular disease events and its mortality. On the contrary, the overweight and obese groups with metabolic abnormalities had significant higher incidence of type 2 diabetes, morbidity and mortality of cardiovascular diseases.

OBJECTIVES: To understand the psychological status of the staff in a general hospital during the coronavirus disease 2019 and its influential factors, and to provide references for the mental health services to hospital staff. METHODS: Using star platform of questionnaire, the staff in the general hospital were investigated via Depression, Anxiety, Stress Scale (DASS-21), Social Support Rating Scale (SSRS) and Simplified Coping Style Questionnaire (SCSQ). The influential factors were discussed by descriptive analysis, rank sum test, single factor analysis, correlation analysis and multiple factors binary logistic regression analysis. RESULTS: A total of 2 060 valid questionnaires were collected. The negative emotions of nurses and cleaners were the most obvious. The depression scores, anxiety scores and stress scores for nurses and cleaners were 5.06±7.47, 6.36±7.84, 9.75±8.65, and 6.72±8.84, 4.51±6.56, 9.69±9.56, respectively. Multivariate binary logistic regression analysis showed that staff types, education levels, job status, economic situation and concerns on the supplies of protective goods were the main influential factors for depression; staff types, contacting status with infected patients, economic situation, concerns on the supplies of protective goods, history of disease were the main influential factors for anxiety; contacting status with infected patients, economic situation, concerns on the supplies of protective goods were the main influential factors for stress. CONCLUSIONS There are differences in psychological characteristics among different groups of staff in the general hospital under the outbreak. Thus psychological protection and intervention measures should be formulated according to different groups and work status.
Adaptation, Psychological ; Anxiety ; diagnosis ; Betacoronavirus ; China ; Coronavirus Infections ; psychology ; Cross-Sectional Studies ; Depression ; diagnosis ; Disease Outbreaks ; Hospitals, General ; Humans ; Pandemics ; Personnel, Hospital ; psychology ; Pneumonia, Viral ; psychology ; Stress, Psychological ; Surveys and Questionnaires

Objective: : To explore the effect of PD-1 gene knockout by CRISPR/Cas9 system on the proliferation and IFN-γ secretion in human T cells. Methods: : The sequence of sgRNA targeting PD-1 was designed. The PD-1-sgRNA and Cas9 mRNA were synthesized by T7 RNApolymerase in vitro, and then the mixture of PD-1-sgRNAand Cas9 mRNAwas delivered into activated T cells by nucleofection. The efficiency of gene knockout was confirmed by sequencing. The phenotypes of T lymphocytes and the expression of PD-1 after gene knockout were analyzed by Flow cytometry. The proliferation of T lymphocytes was calculated by trypan blue counting. The level of IFN-γ secreted by T lymphocytes was detected by ELISA. Results： ：PD-1-sgRNA and Cas9 mRNA were successfully synthesized in vitro and delivered into T cells by nucleofection. Sequencing technology confirmed that the PD-1 gene sequence was edited and the editing efficiency was 58.3%. The expression of PD-1 on T lymphocyte surface was down-regulated successfully by CRISPR/Cas9 system [(9.6±1.85)% vs (16.2±2.05)%, P<0.05]. The knockout of PD-1 gene did not affect the proliferation and phenotype of T lymphocytes(P<0.05); However, compared with the control group, the level of IFN-γ secreted by T lymphocytes in the PD-1sgRNA group was significantly increased (P<0.01). Conclusion: : CRISPR/Cas9 system can successfully ablate PD-1 gene in human T lymphocytes, which could block the negative regulation of PD-1／PD-L1 and further promote the IFN-γ secretion in T cells.

Objective To explore the influence of lifestyle intervention on long-term diabetes in subjects with impaired glucose tolerance (IGT) returned to normal glucose tolerance (NGT) within 6 years.Methods A total of 577 subjects (aged 25-74 years old) with IGT in Daqing were enrolled and randomly assigned to control,and diet,exercise and diet plus exercise groups in a six-year intervention trial in 1986.Subjects who were non-diabetic at the end of the intervention were followed up for additional 14 years.Results Among all the subjects,41.38％ of them who had returned to NGT from IGT within 6 years maintained NGT status after 20 years,and had a lower incidence of diabetes than subjects maintained IGT status (46.55％ vs.75.25％).Of note,in the intervention group,the percentage of participants developed diabetes in the NGT subjects was significantly lower than that in the IGT group (43.71％ vs.76.25％) after 20 years.There was high long-term risk for diabetes in the IGT subjects after the adjustment of age,sex and baseline glucose (HR=1.81,95％CI 1.27-2.58,P=0.001),whereas in the non-intervention group,no significant difference could be viewed in long-term diabetic risk between subjects maintained IGT status and those returned to NGT (71.43％ vs.65.22％) after adjusting of the same confounders (HR=1.03,95％CI 0.45-2.35,P=0.94).Conclusions IGT subjects who had returned to NGT in early years had lower risk for future diabetes than those who remained IGT.However,this beneficial effect could only be viewed in the intervention group,but not in the non-intervention group.

Objective? To explore the effects of family participation in the respiratory rehabilitation of the patients with chronic obstructive pulmonary disease (COPD) in terms of their treatment compliance and outcomes. Methods? Totally 80 COPD patients admitted in The First Affiliated Hospital of Guangzhou Medical University from March 2016 to August 2017 were selected and divided into the control group (n=40) and the observation group (n=40) according to the random number table. Patients in the control group received conventional respiratory rehabilitation intervention, while the patients had their family members participated in the rehabilitation process in the observation group. Treatment compliance and effects were compared between the two groups. Results? The compliance of the observation group totaled 97.50%, while that of the control group totaled 87.50% (χ2=7.207, P＜ 0.05). After 3 months' intervention, the walking distance within 6 min of the observation group was (278.72±45.89) m; the PEF pred% was (93.46±13.47)%; and FEV1% was (87.42±14.71)%, better than those of the control group (t=4.127,7.156,3.859;P＜ 0.05). Conclusions? Family participation in respiratory rehabilitation process can improve the compliance of COPD patients significantly, thus improve the treatment effects, which is worth promoting in clinical practice.

Objective To investigate the difference of apparent diffusion coefficients (ADCs) changes in three major salivary glands after gustatory stimulation using two different stimuli. Methods Thirty healthy volunteers were examined with a 1.5 T MR unit. A diffusion-weighted MR imaging (MR DWI) sequence was performed once at rest and continuously repeated 13 times after gustatory stimulation using a commercially available lemon juice and vitamin C tablets in the same volunteer by using self-controlled method. The subsequence of two stimuli was random. In addition, the salivary flow rates at rest and after stimulation were measured. Characteristics and differences in ADCs curves of three salivary glands before and after stimulation between two stimuli were analyzed. Comparison of maximum ADCs, maximum ADCs increase rates (IRs) and times to maximum ADCs(Tmax) between two stimuli was performed by using independent-samples t test. Correlation analysis between rest salivary flow rates and rest ADCs, the maximum salivary flow rates and ADCs after stimulation, the maximum salivary flow IRs and ADC IRs after stimulation were performed by using Pearson correlation test. Results In lemon juice stimulation group, the mean ADCs mostly showed a steady increase to peak values during the first DW MRI scan after stimulation in all glands, followed by a gradually decrease fluctuating slightly around the baseline values. In vitamin C stimulation group, the mean ADCs were significantly increased in all glands during the first DW MRI scan after stimulation, followed by a gradual upward trend till peak values. In lemon juice stimulation group, the mean Tmax of submandibular and sublingual glands[(184±122)s, (345±232)s, respectively] were significantly earlier than those[(454 ± 301)s, (528 ± 297)s, respectively] in vitamin C stimulation group (t=-3.517 and-2.548 respectively, P<0.01 for all). The mean maximum ADCs of three glands in lemon juice stimulation group[(1.05 ± 0.12) × 10-3 mm2/s, (1.22 ± 0.10) × 10-3 mm2/s and (1.26 ± 0.21) × 10-3 mm2/s, respectively] were all lower than those in vitamin C stimulation group[(1.13±0.13) ×10-3 mm2/s, (1.32±0.25) × 10-3 mm2/s and (1.57 ± 0.36) × 10-3 mm2/s, respectively], and the differences in parotid and sublingual glands between two groups were significant(t=-2.894 and-3.681 respectively, P<0.01 for all). The mean maximum ADC IRs of three glands in lemon juice stimulation group[(11.35±4.07)%, (8.81±5.40)%, (34.08±21.66)%, respectively] were significantly lower than those[(17.80 ± 12.72)%, (18.16 ± 18.93)%, (67.49 ± 46.04)% , respectively] in vitamin C stimulation group (t=-2.252,-2.330 and-3.432 respectively, P<0.05 for all) . In two groups, the mean maximum ADC IRs of parotid and submandibular gland were all significantly lower than sublingual gland (t=-5.994 and-6.443 respectively, P<0.01 for all). No correlation was observed between ADCs and salivary flow rates, ADC IRs and salivary flow rate IRs in two groups (P>0.05). Conclusion MR DWI with transient stimulation using lemon juice is more stable for evaluating the physiologic changes of salivary glands in vivo.

Objective:To investigate the Migration ability toward human pancreatic carcinoma cell line and human colon carcinoma cell line with difference HSP 70 plasma membrane expression .Methods: CD3-CD56+NK cells were obtained from human peripheral blood mononuclear(PBMC)in stem cell growth medium SCGM,2μg/ml TKD was added to the medium on 10th day,the ac-tivating receptor CD94/NKG2C expression levels on NK cells was detected with FAC after 4 days.The human pancreatic carcinoma cell line Colo357 and the human colon carcinoma cell line CW 2 were separated into Colo+and CW2+with high HSP70 expression and Colo-and CW2-with low HSP70 expression;Migration assays of NK to the four difference cell lines were performed in a Transwell cell culture system.The cytolytic activity of TKD-activated NK cells against the four subline with HSP 70 expression on their cell surface was analyzed by MTT assay.Results:Flow cytometry analysis showed that CD 3-CD56+NK cells could expanded after 2 weeks in SCGM medium,and the largest percentage of NK cell was (92.50 ±1.25 )%.CD94 expression levels on NK cells increased obviously after TKD inducement the cell surface HSP 70 expression of Colo+, Colo-were ( 78.2 ±2.2 )% and ( 27.3 ±1.2 )% separately , the cell surface HSP70 expression of CW2+,CW2-were (91.1±2.5)%and (18.2±1.0)%separately after FACS;the Migration of NK cells toward Colo+was (68.6±2.8)%,higher than the migration toward Colo-with (22.8±1.5)%;the Migration of NK cells toward CW2+was(73.5±2.7)%,higher than the migration toward CW2-with (18.2±1.3)%;the cytolytic activity of NK against Colo +was(61.2± 3.0)%compared to (24.5 ±1.5)%against Colo-when the ratio of effector cells and target cell was 20 ∶1,the cytolytic activity of NK against CW2+was (63.8±3.2)%compared to (22.4±1.8)% against CW2-when the ratio of effector cells and target cell was 20∶1.Conclusion:TKD-activated NK cells are highly efficient cytolytic effector cells which have stronger significant migration toward HSP70-positive tumor target cells on their cell surface in vitro .

Objective:To investigate the antitumor effect of TKD-activated NK cells on tumor growth inhibition of human pancreatic carcinoma in nude mice .Methods:CD3-CD56+NK cells were obtained from human peripheral blood mononuclear ( PBMC) in stem cell growth medium SCGM , 2 μg/ml TKD was added to the medium on day 10.The activating receptor CD 94/NKG2C expression levels on NK cells was detected with FAC after 4 days.The cytolytic activity of TKD-activated NK cells against human pancreatic carcinoma subline with HSP 70 expression on their cell surface was analyzed by MTT assay .Established a new model of orthotopic-transplantation tumor of human pancreas .NK cells were injected i.v.into the tail vein of tumor-bearing mice on day 15,the antitumor activity of the NK were evaluated .The capacity to infiltrate Colo 357 tumors in SCID/beige mice was detected with Immunohis-tochemistry.Results:Flow cytometry analysis showed that CD3-CD56+NK cells could expanded in SCGM medium ,and the average percentage of NK cell was (87.50 ±1.35 )%.CD94 expression levels on NK cells increased obviously ,the mean fluorescence intensity of CD94 was(220.56±1.82),compared to (68.72±1.85)of control group cell.The cytolytic activity against HSP70 membrane-positive pancreatic carcinoma sublines Colo 357 cells was high and there was significantly statistical difference between TKD-activated NK cells and unactivated NK cells.The cytolytic activity was(68.72±2.55)%when ratio of effector cells and target cell was 40:1.TKD-activated NK cells had a stronger suppressive effect on tumor growth in BALB /c nude mice bearing Colo 357 cells in vivo ,Median inhibitory rates was ( 61.3 ±1.5 )% .There was significant statistical difference compare to control group ( P <0.01 ) .The result of Immunohistochemistry indicated that predominantly NK cells induced with TKD had the capacity to infiltrate Colo 357 tumors in SCID/beige mice.Conclusion: TKD-activated NK cells are highly efficient cytolytic effector cells which have a stronger significant suppression against pancreatic carcinoma growth in vivo .