The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; Incidence

Objective: To explore the impacts of socio-demographic and clinical co-variates on treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitor (TKI) and identified the predictive models for them. Methods: Data of newly diagnosed adult patients with CML-CP receiving first-line TKI and having complete socio-demographic data and clinical information were reviewed. Cox model was used to identify the independent variables associated with complete cytogenetic response (CCyR) , major molecular response (MMR) , molecular response 4 (MR(4)) and molecular response 4.5 (MR(4.5)) , as well as failure-free survival (FFS) , progression-free survival (PFS) , overall survival (OS) and CML-related OS. Results: A total of 1414 CML-CP patients treated with first-line imatinib (n=1176) , nilotinib (n=170) or dasatinib (n=68) were reviewed. Median age was 40 (18-83) years and 873 patients (61.7% ) were males. Result of the multivariate analysis showed that lower educational level (P<0.001-0.070) and EUTOS long-term survival intermediate or high-risk (P<0.001-0.009) were significantly associated with lower cumulative incidences of CCyR, MMR, MR(4) and MR(4.5), as well as the inferior FFS, PFS, OS and CML-related OS. In addition, those who were males, from rural households, had white blood cells (WBC) ≥120×10(9)/L, hemoglobin (HGB) <115 g/L and treated with first-line imatinib had significantly lower cumulative incidences of cytogenetic and/or molecular responses. Being single, divorced or widowed, having, rural household registration, WBC≥120×10(9)/L, HGB<15 g/L, and comorbidity (ies) was significantly associated with inferior FFS, PFS, OS, and/or CML-related OS. Thereafter, the patients were classified into several subgroups using the socio-demographic characteristics and clinical variables by cytogenetic and molecular responses, treatment failure and disease progression, as well as overall survival and CML-related OS, respectively. There were significant differences in treatment responses and outcomes among the subgroups (P<0.001) . Conclusion: Except for clinical co-variates, socio-demographic co-variates significantly correlated with TKI treatment responses and outcomes in CML-CP patients. Models established by the combination of independent socio-demographic and clinical co-variates could effectively predict the responses and outcome.
Adult ; Antineoplastic Agents/therapeutic use* ; Dasatinib/therapeutic use* ; Demography ; Humans ; Imatinib Mesylate/therapeutic use* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Male ; Protein Kinase Inhibitors/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Brucella ; Brucellosis/diagnosis* ; Chromatography, Affinity ; Gold Colloid ; Humans

OBJECTIVES: To study the value of functional echocardiographic parameters in predicting refractory septic shock in neonates. METHODS: A total of 72 neonates with septic shock were enrolled. According to the highest value of septic shock score, they were divided into two groups: refractory (n=30) and non-refractory (n=42). The two groups were compared in terms of clinical data, laboratory findings, and functional echocardiographic parameters. The receiver operating characteristic (ROC) curve was used to evaluate the performance of functional echocardiographic parameters in predicting refractory septic shock. RESULTS: Compared with the non-refractory group, the refractory group had significantly lower cardiac output and cardiac index (CI) and a significantly higher mean arterial pressure (MAP)/CI ratio (P<0.05). CI had a cut-off value of 2.6 L/(min·m²), a sensitivity of 79%, a specificity of 83%, and an area under the ROC curve (AUC) of 0.841 in predicting septic shock-related death (P<0.05), and MAP/CI ratio had a cut-off value of 11.4, a sensitivity of 83%, a specificity of 73%, and an AUC of 0.769 (P<0.05). CI had a cut-off value of 2.9 L/(min·m²), a sensitivity of 69%, a specificity of 69%, and an AUC of 0.717 in predicting all-cause death within 28 days (P<0.05). CONCLUSIONS CI and MAP/CI ratio can be useful for early prediction of septic shock-related death in neonates.
Infant, Newborn ; Humans ; Shock, Septic/diagnostic imaging* ; Echocardiography ; ROC Curve

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

BACKGROUND: Cumulative blood pressure (BP), a measure incorporating the level and duration of BP exposure, is associated with the risk of cardiovascular disease (CVD). However, the level at which cumulative BP could significantly increase the risk remains unclear. This study aimed to investigate the association of 15-year cumulative BP levels with the long-term risk of CVD, and to examine whether the association is independent of BP levels at one examination. METHODS: Data from a 26-year follow-up of the Chinese Multi-provincial Cohort Study-Beijing Project were analyzed. Cumulative BP levels between 1992 and 2007 were calculated among 2429 participants free of CVD in 2007. Cardiovascular events (including coronary heart disease and stroke) occurring from 2007 to 2018 were registered. Adjusted hazard ratios (HRs) for CVD incidence associated with quartiles of cumulative systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated. RESULTS: Of the 2429 participants, 42.9% (1042) were men, and the mean age in 2007 was 62.1 ± 7.9 years. Totally, 207 CVD events occurred during the follow-up from 2007 to 2018. Participants with higher levels of cumulative SBP or DBP exhibited a higher incidence rate of CVD (P < 0.001). Compared with the lowest quartile of cumulative SBP, the HR for CVD was 1.03 (95% confidence interval [CI]: 0.59-1.81), 1.69 (95% CI: 0.99-2.87), and 2.20 (95% CI: 1.21-3.98) for the second to the fourth quartile of cumulative SBP, and 1.46 (95% CI: 0.86-2.48), 1.99 (95% CI: 1.18-3.35), and 2.08 (95% CI: 1.17-3.71) for the second to the fourth quartile of cumulative DBP, respectively. In further cross-combined group analyses with BP measurements in 2007, 15-year cumulative BP levels higher than the median, that is, 1970.8/1239.9 mmHg·year for cumulative SBP/DBP, which were equivalent to maintaining SBP/DBP levels of 131/83 mmHg or above on average in 15 years, were associated with higher risk of CVD in subsequent years independent of BP measurements at one-time point. CONCLUSION Cumulative exposure to moderate elevation of BP is independently associated with increased future cardiovascular risk.
Aged ; Asian Continental Ancestry Group ; Blood Pressure/physiology* ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Cohort Studies ; Humans ; Hypertension/epidemiology* ; Incidence ; Male ; Middle Aged ; Risk Factors

Objective To investigate the status of self‐management of blood pressure (BP) among elderly hypertensive patients living in new rural communities of Shanghai. Methods We enrolled a total of 2 241 hypertensive patients over 60 years old who participated in the National Key Research and Development Project "Cohort study on hypertension" of the 13th Five‐Year Plan in Langxia, Shanghai from May to July 2018. Questionnaires, physical examinations, and laboratory tests were conducted. We collected participants' demographic information, cardiovascular history, and self‐management behaviors related to hypertension. The status of self‐management of BP among participants with hypertension was analyzed. Pearson's chi‐squared test was used to explore the differences between males and females. Results Participants'mean age was (70.0±6.8) years, and males accounted for 38.8% of all participants. The systolic and diastolic BP levels of participants were (147.8±15.4) mmHg (1 mmHg=0.133 kPa) and (82.8±9.8) mmHg, respectively. The systolic blood pressure level of women was higher than that of men, and the diastolic blood pressure level of men was higher; the difference was statistically significant (all P<0.05). The awareness, treatment, and control rate of hypertension were 79.0%, 78.0%, and 25.6%, respectively. Males had a significantly higher control rate than females (P<0.05). The status of self‐management of blood pressure was as follows: (1) As to lifestyle, 84.4% of participants lacked exercise, and 69.2% were overweight or obese. The prevalence of smoking and drinking was higher in males (40.7% and 46.2%, respectively), and the proportion of females (12.4%) with anxiety and/or depression was higher than that of males (P all<0.001). (2) Concerning BP‐monitoring, only 10.1% of participants measured BP every week, 22.9% had BP measurement instruments at home, and 4.6% recorded their BP levels. There was no significant difference in self‐blood pressure monitoring behavior between men and women. (3) Regarding adherence to medication treatment, 97.6% took antihypertensive drugs regularly, and 21.6% were on combination therapy. The proportion of men taking combined drugs was higher than that of women, but there was no significant difference. Conclusions The rates of awareness, treatment, and control of hypertension in elderly hypertensive patients in new rural communities of Shanghai were above the national average. However, the status of self‐management of BP was still not satisfactory. More attention should be paid to healthy lifestyle, home BP monitoring, and effective pharmaceutical treatment strategies for hypertension.

Sangzhi alkaloids (SZ-A) are derived from traditional Chinese medicine Ramulus Mori, serving well as an innovative antidiabetic drug, due to α-glucosidase inhibition. To evaluate the potency of glucosidase inhibitory effect of SZ-A, the enzyme-based screening platforms, including sucrase, maltase and amylase were established, and IC₅₀ was calculated. The effects of SZ-A on postprandial blood glucose at a single dose, oral sucrose, starch and glucose loading were determined in normal ICR mice and alloxan-induced hyperglycemic mice. To confirm the anti-diabetic effects of SZ-A on glucose and lipid metabolism after long-term administration, the postprandial and fasting blood glucose, serum insulin, urinary glucose levels, glycosylated serum proteins and blood lipid levels were determined in high-fat fed C57 obese mice (pre-diabetic HFC57 mice) and diabetic rats induced by streptozotocin (STZ). The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. We found that SZ-A exhibited a significant inhibitory effect on the sucrase and maltase. SZ-A showed no effect on amylase. In normal ICR mice and alloxan-induced hyperglycemic mice, SZ-A at a single dose significantly delayed and reduced the peak of blood glucose after sucrose or starch loading, but showed no effect on the increase of blood glucose after glucose loading. In STZ diabetic rats, SZ-A significantly reduced the postprandial or fasting blood glucose levels, glycosylated serum proteins and urinary glucose. SZ-A also reduced serum triglyceride (TG) and cholesterol (TC) levels after 3 weeks of treatment. SZ-A ameliorated the postprandial blood glucose or the fasting blood glucose elevation, and reduced the incidence of hyperglycemia in HFC57 mice. SZ-A decreased the basal insulin level, improved insulin sensitivity, and ameliorated glucose intolerance in pre-diabetic HFC57 mice. Our results indicated that SZ-A had a novel inhibitory activity on α-glucosidase, especially on disaccharidases. SZ-A at a single dose significantly reduced the peak of blood glucose elevation and delayed the increase of blood glucose in normal and diabetic mice after disaccharide and polysaccharide loading. Long-term SZ-A treatment improved glucose and lipid metabolic profiles by delaying carbohydrate absorption from the intestine and reduced the postprandial blood glucose levels in both pre-diabetic and diabetic animal models. Therefore, SZ-A application may display a beneficial role in preventing the development and complications of diabetes.

While it is known that spermatogonial stem cells (SSCs) initiate the production of male germ cells, the mechanisms of SSC self-renewal, proliferation, and differentiation remain poorly understood. We have previously identified Strawberry Notch 1 (SBNO1), a vertebrate strawberry notch family protein, in the proteome profile for mouse SSC maturation and differentiation, revealing SBNO1 is associated with neonatal testicular development. To explore further the location and function of SBNO1 in the testes, we performed Sbno1 gene knockdown in mice to study the effects of SBNO1 on neonatal testicular and SSC development. Our results revealed that SBNO1 is required for neonatal testicular and SSC development in mice. Particularly, in vitro Sbno1 gene knockdown with morpholino oligonucleotides caused a reduction of SSCs and inactivation of the noncanonical Wnt pathway, through Jun N-terminal kinases. Our study suggests SBNO1 maintains SSCs by promoting the noncanonical Wnt pathway.
Adult Germline Stem Cells/metabolism* ; Animals ; Cell Proliferation/physiology* ; Gene Knockdown Techniques ; Male ; Mice ; Proteome ; Repressor Proteins/metabolism* ; Testis/metabolism* ; Wnt Signaling Pathway/physiology*