[A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China].

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

[Clinical observation of superior rectus transposition with/without augmented suture and vertical rectus transposition for the treatment of strabismus caused by complete abducens nerve palsy].

Objective: To evaluate the efficacy and safety of superior rectus transposition (SRT) with/without augmented suture and vertical rectus transposition (VRT) for the treatment of strabismus caused by complete abducens nerve palsy. Methods: This was a retrospective cohort study. Forty-two patients (42 eyes) with complete abducens nerve palsy underwent strabismic surgeries from January 2015 to November 2020 in Tianjin Eye Hospital. According to the different procedures, the patients were divided into three groups: SRT group (16 cases, SRT with medial rectus recession), superior rectus transposition with augmented suture (SRTA) group (13 cases, SRT with Buckley suture and medial rectus recession) and VRT group (13 cases). The preoperative and postoperative (1, 6 and 12 months) data including deviations, ocular motility, binocular vision and surgical complications among three groups were analyzed and compared. χ2 test was used for comparison of count data among three groups. The measurement data were compared among three groups by the repeated measures ANOVA. LSD-t test was used for within-group comparison and between-group comparison. Results: There was no difference in sex ratio, age and course of disease among the groups (all P>0.05). The horizontal deviations of the three groups at 1, 6 and 12 months after surgeries was lower than that before surgeries, and the difference was statistically significant (all P<0.001). The horizontal deviations of the SRT group, SRTA group and VRT group at 12 months after surgeries were (+0.8±5.8), (+0.8±4.5), (+1.2±2.5) prism diopters (PD), respectively, lower than that of the preoperative (+82.8±17.2), (+77.7±26.1), (+71.5±18.6) PD. However, there was no significant difference among different postoperative follow-up timepoints (all P>0.05). There was no difference in horizontal deviations before surgeries and at 1, 6 and 12 months after surgeries among three groups (P>0.05). There were significant differences in the scales of abduction motility among preoperative, postoperative 1, 6 and 12 months measurements for three group (all P<0.001). The scales of abduction before surgeries in the SRT group, SRTA group, and VRT group were (-4.4±0.5), (-4.4±0.5), (-4.5±0.5) scale and at 12 months after surgeries were (-2.3±0.7), (-2.2±0.5), (-2.1±0.6) scale respectively. But there was no change among different postoperative follow-up timepoints (all P>0.05). Preoperative and postoperative 1-, 6-and 12-month abduction motility was similar among three groups (P>0.05). There were significant differences in the scales of adduction limitation among preoperative, postoperative 1-, 6-and 12-months measurements for three group (all P<0.05). But there was no change among different postoperative follow-up timepoints (all P>0.05). There were significant differences between the SRT group [(-0.9±0.6), (-0.8±0.6) scale] and the SRTA groups [(-1.5±0.5), (-1.4±0.5) scale] (t=-2.62, -2.52) and between the SRTA group and the VRT group [(-0.8±0.8), (-0.6±0.7) scale] (t=2.62, 3.01) at 6 and 12 months after surgeries (all P<0.05). The outcomes of binocular vision at postoperative 12 months were similar among three groups (P>0.05). No patient had torsional diplopia and anterior segment ischemia. Only 2 patients from the SRTA group had hypotropia of 4 to 5 PD in the primary position associated with supraduction limitation. Conclusions: SRT with/without augmented suture and VRT are effective and safe procedures for the treatment of strabismus caused by complete abducens nerve palsy. They could correct deviations, improve abduction motility and restore binocular vision, with stable outcomes and a small risk of vertical and torsional diplopia.

Assessment of the effects of human activity and natural condition on the outflow of Syr Darya River: A stepwise-cluster factorial analysis method.

Water scarcity causes a series of eco-environmental problems, such as land salinization, biodiversity reduction and food crisis, which seriously restricts the sustainable development of the Aral Sea basin. In this study, a stepwise-cluster factorial analysis (SCFA) approach is proposed for assessing the effects of natural condition and human activity on the outflow of Syr Darya River (abbreviated as OSR) that has significant effects on the eco-environmental restoration of the Aral Sea. SCFA coupled stepwise cluster analysis and factorial analysis cannot only reflect the variability of outflow, but also identify the driving factors quantitatively. The results disclose that, in 1960-1991, the dominant factors (affecting the OSR) are upstream inflow (25.77%) > agricultural water use of Uzbekistan (7.21%) > industrial water use of Uzbekistan (4.53%) > agricultural water use of Kazakhstan (3.81%) > Precipitation (3.66%); interactions between upstream inflow and agricultural water use of Uzbekistan, Kazakhstan and Tajikistan and interactions between reservoir and evapotranspiration have the significant effects on the OSR. Results also indicate that, in 1992-2015, the dominant factors that affect the OSR are agricultural water use of Uzbekistan (23.31%) > agricultural water use of Kazakhstan (22.15%) > industrial water use of Uzbekistan (8.31%) > domestic water use of Kazakhstan (4.68%) > agricultural water use of Tajikistan (4.54%) > domestic water use of Uzbekistan (4.41%); the interactions between industrial water use and agricultural water use of Uzbekistan, Kazakhstan and Tajikistan and the interactions between reservoir and upstream inflow have the pivotal effects on OSR. In the future, when the agricultural water use of the basin decrease as 4% and the industry water use of Uzbekistan decrease as 2%, the OSR may recover to the middle level of 1970s. The results help identify the major factors affecting the outflow of Syr Darya River as well as seek an effective approach to restore the eco-environment of Aral Sea basin.

Development of an integrated multivariate trend-frequency analysis method: Spatial-temporal characteristics of climate extremes under global warming for Central Asia.

Temperature and precipitation are the two most critical climate variables and their extreme states have more severe impacts than average states on both human society and natural ecosystem. In this study, an integrated multivariate trend-frequency analysis (IMTFA) approach is developed for the risk assessment of climate extremes under the global warming. Through incorporating multiple time series analysis techniques (i.e., M-K test, Sen's slope estimator and Pettitt test) and copula function into a general framework, IMTFA is capable not only of analyzing the temporal trends and change points of extreme temperatures and precipitations, but also of quantifying their univariate and multivariate risks. IMTFA is applied to the Central Asia with considering a long-term (1881-2018) observation data. Our findings are: (i) significant wetting and warming trends were occurred in the Central Asia over past one hundred years, where 42.5%, 59.4% and 79.2% stations have change points for extreme precipitations, maximum and minimum temperatures, respectively; (ii) the occurrences of extreme climate events show obviously spatial heterogeneity, where the highest risks of meteorological drought, flood and frost events are occurred in the southwest, southeast and northeast regions, respectively; (iii) global warming significantly affects the intensities and frequencies of extreme precipitations and temperatures, and their univariate and multivariate risks are intensified in the most regions of Central Asia. The above findings can provide more valuable information for risk assessment and disaster adaptation of climate extremes in Central Asia.

Protective effect of necrostatin-1 on myocardial tissue in rats with acute myocardial infarction.

The aim of this study was to investigate the protective effect of necrostatin-1 on myocardial tissue of acute myocardial infarction (AMI) rats and to provide a basis for necrostatin-1 for the treatment of acute myocardial infarction. AMI rats (45) were established by ligating the anterior descending branch of the left coronary artery. The rats were randomly divided into the model group and necrostatin-1 low-dose and high-dose groups. The control group rats (15) underwent the sham operation. The rats in the necrostatin-1 low-dose and high-dose groups were injected with 1 and 4 mg/kg necrostatin-1, respectively, via the tail vein. The rats in the control and model groups were injected with isometric dimethyl sulfoxide, once daily, for 3 consecutive days. The levels of RIP1 and RIP3 mRNA and phosphorylated protein in the myocardial tissue of rats were detected by real time polymerase chain reaction and western blot. The myocardial infarct size was detected by tetrazolium chloride. Compared with that in the control group, the levels of RIP1 and RIP3 mRNA and phosphorylated protein significantly increased in the myocardial tissue of model group rats, necrostatin-1 low-dose group, and high-dose group. The levels of RIP1 and RIP3 mRNA and phosphorylated protein in the myocardial tissue of rats in the necrostatin-1 low-dose and high-dose groups decreased significantly compared with that in the model group (P < 0.05). The levels of RIP1 and RIP3 mRNA in the myocardium of the high-dose group rats were significantly lower than those of the low-dose group rats (P < 0.05). The myocardial infarct sizes significantly increased in model, low-dose, and high-dose group rats. The apoptotic level of myocardial cells significantly decreased in the low-dose group and high-dose group after treatment with necrostatin-1 but was still higher than that of the control group (P < 0.05). In conclusion, necrostatin-1 can inhibit myocardial tissue apoptosis and necrosis in acute myocardial infarct rats and has a protective effect on myocardial tissue.

Using the attract method to identify core pathways in juvenile idiopathic arthritis.

The aim of this study was to identify core pathways associated with juvenile idiopathic arthritis (JIA) using the attract method. Kyoto Encyclopedia of Genes and Genomes pathways were determined using the GSEA-ANOVA method, based on the gene expression data of JIA. Syn-expression groups within core attractor pathways were identified by hierarchical clustering. Correlated sets of genes exhibiting highly similar profiles to the syn-expression groups were identified and each correlated set was subjected to a gene ontology functional enrichment analysis to discover potentially shared biological themes. Based on a false-discovery rate < 0.05, we identified 11 significant pathways were identified as potential attractors. Flag genes or uninformative genes were removed and 5 discriminative pathways: the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were identified. A final set of syn-expression groups with a consistent trend of relative expression of pathway-related genes was obtained; that is, the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were composed of 2, 2, 1, 2, and 3 clusters, respectively. Genes in each correlated set shared common roles, and changes at the pathway level were more likely to be real. In light of these, the attract method was able to on expand important context to find distinguishing expression patterns within pathways. This paper predicted that the functional themes involved in protein synthesis (such as proteasome, ribosome, spliceosome) were closely related to the progression of JIA, which might contribute to the detection of therapy target for JIA.

Effects of Sirtuin 1 on the proliferation and osteoblastic differentiation of periodontal ligament stem cells and stem cells from apical papilla.

The function of SIRT1 in the proliferation and osteoblastic differentiation of dental stem cells is unclear. The aim of this study was to assess the roles of SIRT1 in these processes using periodontal ligament stem cells (PDLSCs) and stem cells from apical papilla (SCAPs). A defined concentration of resveratrol, an SIRT1 activator, or nicotinamide, an SIRT1 inhibitor, was administered to PDLSCs, SCAPs, and a mixed group of the two cell lines, and their effects on these processes analyzed. Cell proliferation was tested using microtitration with a tetrazolium dye (MTT). Alkaline phosphatase (ALP) activity, mineralization ability, and the expression of osteoblastic differentiation-associated genes were assessed as well. These studies demonstrated that resveratrol could promote cell proliferation of all three groups in a gradually increasing trend over time. In contrast, nicotinamide suppressed the proliferation of the three cell lines. The results also showed that the markers of osteoblastic differentiation: ALP activity, mineralization ability, and the expression levels of the osteoblastic genes ALP, osteopontin, osteocalcin, and bone sialoprotein, were enhanced in the groups with resveratrol treatment. In contrast, following addition of nicotinamide, ALP activity, mineralization ability, and the expression levels of the osteoblastic genes were down-regulated in the cells. Together, these results suggest that the SIRT1 activator and inhibitor compounds, resveratrol and nicotinamide, function at high efficiency in adjusting cell proliferation, and that SIRT1 is a powerful regulator of osteoblastic differentiation of PDLSCs and SCAPs. In addition, co-culture of the two cell lines could promote their abilities of proliferation and osteogenic differentiation.

Activated natural killer cells accelerate liver damage in patients with chronic hepatitis B virus infection.

Emerging evidence indicates that natural killer (NK) cells may contribute to liver injury in patients with hepatitis B virus (HBV) infection. Because HBV infection progresses through various disease phases, the cytolytic profiles of peripheral and intrahepatic NK cells in HBV-infected patients remain to be defined. In this study, we comprehensively characterized intrahepatic and peripheral NK cells in a cohort of HBV-infected individuals, and investigated their impact on liver pathogenesis during chronic HBV infection. The study population included 34 immune-clearance (IC) patients, 36 immune-tolerant (IT) carriers and 10 healthy subjects. We found that the activity of peripheral NK cells from IC patients was functionally elevated compared to IT carriers and controls, and NK cell activation was indicated by an increased expression of CD69, CD107a, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Further analysis showed that the increased activity of both peripheral and hepatic NK cells was correlated positively with liver injury, which was assessed by serum alanine aminotransferase levels (ALT) and the liver histological activity index (HAI). Interestingly, the frequency of peripheral NK cells was reduced in IC patients (especially those with higher HAI scores of 3-4), but there was a concomitant increase in hepatic NK cells. The functionally activated NK cells are enriched preferentially in the livers of IC patients and skew towards cytolytic activity that accelerates liver injury in chronic hepatitis B (CHB) patients.

Role of interleukin-10 gene polymorphisms in the development of coronary artery disease in Chinese population.

The aim of this study was to investigate the association between three common SNPs (-1082A/G, -819T/C, and -592A/C) in the interleukin 10 (IL-10) gene, and the development of coronary artery disease. Between January 2013 and December 2014, 272 patients with coronary artery disease and control subjects (each) were recruited for this study from the Huaihe Hospital of Henan University. The IL-10-1082A/G, -819T/C and -592A/C gene polymorphisms were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Logistic regression analyses revealed an association between the AA and GA+AA genotypes of IL-10-1082G/A and an elevated risk of coronary artery disease, compared to the GG genotype [adjusted odds ratio (OR) = 2.31 and 1.49; 95% confidence interval (CI) = 1.29-4.19 and 1.04-2.12, respectively]. The AG+GG genotype was associated with a moderately increased risk of coronary artery disease in smokers (adjusted OR = 2.74; 95% CI = 1.01-3.01). In conclusion, the AA and GA+AA genotypes of IL-10-1082G/A were associated with an elevated risk of coronary artery disease; the IL-10-1082G/A gene polymorphism also interacted with the tobacco smoking habits, contributing to the development of coronary artery disease.

Associations between the SRD5A2 gene V89L and TA repeat polymorphisms and breast cancer risk: a meta-analysis.

The 5α-reductase type 2 (SRD5A2) gene plays a significant role in the development of breast cancer. The V89L and TA repeat polymorphisms of the SRD5A2 gene have been considered as risk factors for breast cancer. However, the results have been inconsistent. To resolve this conflict, we performed a meta-analysis of studies with V89L (1144 patients and 808 controls) and with TA repeat genotyping (1952 cases and 1008 controls). The associations were evaluated by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The result showed that there was no relationship between the V89L polymorphism of the SRD5A2 gene (V/V versus V/L + L/L genotypes) and breast cancer susceptibility (OR = 1.21; 95%CI = 0.99-1.47; P = 0.28). In addition, there was no difference between patients with breast cancer and healthy people in the distributions of the L allele (OR = 1.06; 95%CI = 0.75-1.49; P = 0.003). Similarly, no significant association between the SRDA5A2 TA repeat polymorphism and breast cancer risk was discovered. The comparison of (TA)0/(TA)0versus (TA)0/(TA)9 + (TA)9/(TA)9 genotypes found no difference in the risk of breast cancer (OR = 0.91; 95%CI = 0.66-1.25; P = 0.05). The OR for the (TA)0 versus (TA)9 allele was 0.89 (95%CI = 0.67-1.19). In conclusion, the V89L and TA repeat polymorphisms of SRD5A2 gene were found to have no significant associations with breast cancer risk.

Decline in intrahepatic cccDNA and increase in immune cell reactivity after 12 weeks of antiviral treatment were associated with HBeAg loss.

Viral load reduction facilitates recovery of antiviral T-cell responses. Dynamic alterations in intrahepatic viraemia clearance and immune cell reactivity during the early phase of nucleoside analogue (NA) therapy and the impact of these changes on HBeAg seroconversion are unknown. Fifteen HBeAg-positive chronic hepatitis B (CHB) patients were treated with adefovir dipivoxil. T-cell reactivity to HBV core and surface antigens were tested using ELISPOT assay from baseline to week 48 post-treatment (at 4-week intervals). Before and at week 12 of treatment, paired liver biopsies were analysed for intrahepatic HBV-DNA and cccDNA via real-time fluorescent PCR. In situ detection of CD4(+) , CD8(+) T cells and NK cells was analysed by immunohistochemistry. With viral load reduction, HBV-specific IFN-γ-producing CD4(+) T cells in patients with HBeAg loss were greatly enhanced and reached the highest level at week 12, with further increase observed between week 36 and week 48. After 12 weeks of treatment, total intrahepatic HBV-DNA and cccDNA had significantly decreased; however, there was no difference in the viral loads or extent of reduction between patients with and without HBeAg loss. Paralleling reduction in viral load, intrahepatic CD8(+) T lymphocytes increased in patients with HBeAg loss compared with baseline values. Only one patient without HBeAg loss exhibited similar results. Increased immune cells were observed in certain patients along with reduced hepatic viral loads during the second phase of HBV-DNA decline, which could promote the recovery of antiviral immunity and facilitate HBeAg loss.

The risk of bacteria in foam sclerotherapy: does the condition of the air in outpatient vs. operating rooms make a difference?

BACKGROUND: Foam sclerotherapy has been one of the most frequently applied therapeutic methods for the treatment of varicose veins and venous malformation. Few studies have investigated the sterile condition of the air used for foam creation. OBJECTIVES: To evaluate the bacterial conditions in foam created from the air in outpatient and operating rooms used for sclerotherapy treatment, in order to provide the basis for clinical applications in foam sclerotherapy. MATERIALS AND METHODS: In this study, we measured the amount of airborne microorganisms in the air in the operating room, and in the outpatient room, the polidocanol (POL) foam created using the air in the respective rooms, and the microorganisms present in the liquid POL. We used the settle plate method for air sampling. We used the Tessari method to generate foam. The experiment was repeated three times. RESULTS: Typical bacterial colonies were formed on nutrient agar plates in both the outpatient room and operating room air groups. No colonies were cultivated in the liquid POL. Although the use of sterile or nonsterile air in sclerotherapy produces significantly different results in the counts of colony-forming units, there was no difference in the foam created using sterile or nonsterile air (i.e. no colonies were cultivated on either foam). CONCLUSIONS: There is no increased risk of infection when using foam sclerotherapy in outpatient rooms compared with using foam created under sterile operating-room conditions.

Hypericum perforatum L. preparations for menopause: a meta-analysis of efficacy and safety.

OBJECTIVE: To compare by meta-analysis the efficacy and adverse events of Hypericum perforatum L. (St. John's Wort), or its combinations, and placebo for menopausal women. DESIGN: A systematic review and meta-analysis were carried out by searching in Pubmed, Cochrane Library, Embase and the Web of Science database. RESULTS: Extracts of Hypericum perforatum L. and its combination with herbs were significantly superior to placebo (standard mean difference = -1.08; 95% confidence interval -1.38 to -0.77); extracts of Hypericum perforatum L. proved to be more effective than placebo in the treatment of menopause. Adverse events occurred in 53 (17.4%) patients on Hypericum perforatum L. preparations and 45 (15.4%) patients on placebo (relative risk = 1.16; 95% confidence interval 0.81-1.66). CONCLUSION: Extracts of Hypericum perforatum L. have possibly fewer side-effects than placebo for the treatment of menopausal women.

Effects of hypoxia on proliferation and osteogenic differentiation of periodontal ligament stem cells: an in vitro and in vivo study.

Changes in oxygen concentration may influence various innate characteristics of stem cells. The effects of varying oxygen concentration on human periodontal ligament stem cells (HPDLSCs) has not been explored, particularly under hypoxia-related conditions. First, HPDLSCs were cultured from the periodontium of human teeth using the outgrowth method. STRO-1 and CD146 expression of HPDLSCs was investigated by flow cytometry. To detect the multilineage differentiation capacities of HPDLSCs, osteogenic-like and adipogenic-like states were induced in cells. Next, HPDLSCs (passage 3) were exposed to normal oxygen (21% O2) or hypoxia (2% O2) conditions for 7 days and cell proliferation was evaluated. After culture in osteogenic medium for 7 days, osteoblastic differentiation was evaluated by semi-quantitative reverse transcription-polymerase chain reaction analysis to detect 3 osteoblastic markers: core-binding factor a 1/runt-related transcription factor 2, osteocalcin, and osteopontin. In addition, each cell group was incubated with a hydroxyapatite/tricalcium phosphate carrier and transplanted subcutaneously into the back of immunocompromised mice to investigate transplantation differences in vivo. HPDLSCs were isolated, cultured, and successfully identified. After exposure of HPDLSCs to hypoxia for 7 days, the proliferation rate was increased and showed higher osteogenic differentiation potential compared to control cells. After 12 weeks of transplantation, hypoxia-treated HPDLSCs differentiated into osteoblast-like cells that formed bone-like structures. These results suggest that oxygen concentrations affect various aspects of HPDLSC physiology and that hypoxia enhances osteogenic differentiation both in vivo and in vitro. Oxygen concentration may be a critical parameter for HPDLSCs during expansion and differentiation.

[Cardiovascular diseases burden attributed to low physical activity in China, 1990-2019].

Objective: To analyze the burden of cardiovascular disease (CVD) attributed to low physical activity (LPA) and its changing trends in China from 1990 to 2019. Methods: On the basis of the province results of the Study of Global Burden of Disease 2019 in China, we described the distribution of CVD death and disability-adjusted life year (DALY) attributed to LPA by sex, age and province. Joinpoint 4.9.1.0 was used to calculate the average annual percentage change. Results: In 2019, the number of CVD deaths and DALY attributed to LPA in people aged ≥25 years were 0.127 million and 1.863 million person-years in China, respectively, The age-standardized mortality rate (ASMR) and standardized DALY rate of CVD attributed to LPA were slightly higher in men than in women, and much higher in ischemic heart disease patients than in ischemic stroke patients. The ASMR (8.85/100 000) and the standardized DALY rate (112.34/100 000) of CVD attributed to LPA in China in 2019 showed no obvious change compared with 1990, while decreased in the last decade. The largest increases in the mortality rate and DALY rate were observed in people aged ≥75 years from 1990 to 2019 (26.89%, 15.61%), but the mortality rate and DALY rate in people aged 60-74 years showed a decreasing trend. The mortality rate and DALY rate in men aged 25- 44 years showed the largest increases (37.50%, 35.49%), while women aged ≥75 years had the largest increases (31.00%, 18.02%). In 2019, the highest ASMR and standardized DALY rate of CVD attributed to LPA were found in Jilin, Inner Mongolia and Hebei. The largest increases were found in Qinghai (182.41%, 154.70%), Gansu (181.29%, 152.77%), and Chongqing (132.01%, 102.79%) and the largest decreases were found in Beijing (59.11%, 62.09%), Macau (41.89%, 39.37%) and Guangdong (36.93%, 40.72%) from 1990 to 2019. Conclusion: The disease burden of CVD attributed to LPA in China was quite high and showed gender, age and area specific differences.

Overexpression of microRna-200c in CD44+CD133+ CSCS inhibits the cellular migratory and invasion as well as tumorigenicity in mice.

Cancer stem cells (CSCs) are believed to be responsible for drug resistance, metastasis of tumors. To investigate the biological characteristics of CD44+CD133+CSCs with over- expressing microRNA-200c (miR-200c), and to provide evidences for miR-200c as a tumor suppressor to treat melanoma. CD44+CD133+CSCs were isolated from the mouse melanoma B16F10 cell line by using immune magnetic activated cell sorting. The lentivirus miR-200c was transduced into the cells, and the effect of miR-200c overexpression on the biological characteristics of B16F10 CD44+ CD133+CSCs was analyzed by a series assays. The stable overexpression of miR-200c in B16F10 CD44+CD133+CSCs obviously resulted in downregulation of zinc-finger E-box binding homeobox 1 expression, reduction of the cell proliferation, colony forming, cell migratory and invasion ability in vitro as well as tumorigenicity in vivo compared with those of the B16F10 cells and B16F10 non-CD44+ CD133+CSCs. These findings suggest that the miR-200c overexpression as a novel strategy to target therapy of melanoma CSCs.

Nitrogen-corrected True Metabolizable Energy and Amino Acid Digestibility of Chinese Corn Distillers Dried Grains with Solubles in Adult Cecectomized Roosters.

This study was conducted to evaluate chemical composition, nitrogen-corrected true metabolizable energy (TMEn) and true amino acids digestibility of corn distillers dried grains with solubles (DDGS) produced in China. Twenty five sources of corn DDGS was collected from 8 provinces of China. A precision-fed rooster assay was used to determine TMEn and amino acids digestibility with 35 adult cecectomized roosters, in which each DDGS sample was tube fed (30 g). The average content of ash, crude protein, total amino acid, ether extract, crude fiber and neutral detergent fiber were 4.81, 27.91, 22.51, 15.22, 6.35 and 37.58%, respectively. TMEn of DDGS ranged from 1,779 to 3,071 kcal/kg and averaged 2,517 kcal/kg. Coefficient of variation for non-amino acid crude protein, ether extract, crude fiber and TMEn were 55.0, 15.7, 15.9 and 17.1%, respectively. The average true amino acid digestibility was 77.32%. Stepwise regression analysis obtained the following equation: TMEn, kcal/kg = -2,995.6+0.88×gross energy+49.63×a* (BIC = 248.8; RMSE = 190.8; p<0.01). Removing gross energy from the model obtained the following equation: TMEn, kcal/kg = 57.88×ether extracts+87.62×a* (BIC = 254.3, RMSE = 223.5; p<0.01). No correlation was found between color scores and lysine true digestibility (p>0.05). These results suggest that corn DDGS produced in China has a large variation in chemical composition, and gross energy and a* value can be used to generate TMEn predict equation.

Partial cellular reprogramming stably restores the stemness of senescent epidermal stem cells.

OBJECTIVE: Adult stem cell senescence and exhaustion are important drivers of organismal age. Restored stem cell self-renewal has revealed novel therapeutic targets for decreasing the incidence of age-associated diseases (AADs) and prolonging the human health span. Transient ectopic expression of the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc (collectively known as OSKM) in somatic cells can induce partial cellular reprogramming and effectively ameliorate their age-associated hallmarks. However, how this form of rejuvenation is applied to senescent stem cells remains unknown. MATERIALS AND METHODS: The Integrin-α6highCD71high epidermal stem cells (ESCs) with low self-renewal ability were sorted by flow cytometry and then treated by the interrupted reprogramming induced by transient expression of OSKM. The ability of secondary clones' generation and self-proliferation in vitro, as well as stem cell marker p63, were detected to determine their self-renewal ability. Besides, gene and protein of epidermal cell markers were detected to determine whether their cell identities were retained. Finally, DNA methylation age (eAge) and DNA dehydroxymethylase/methyltransferase were analyzed to explore the alternation of their global DNA methylation pattern during this rejuvenation. RESULTS: The partial reprogramming restored the youthful self-renewal and proliferation in senescent ESCs, including larger secondary clone generation, higher expression of stem cell marker p63 and proliferation marker Ki67, and faster proliferation speed, in each case without abolishing epithelial cellular identity. Moreover, the rejuvenation of adult stem cells could be maintained for 2 weeks after reprogramming factor withdrawal, which was more stable than that of differentiated somatic cells. Additionally, we found that partial reprogramming counteracted the acceleration of eAge in senescent epidermal stem cells and DNA methyltransferase 1 (DNMT1) may play a crucial role in this process. CONCLUSIONS: Partial reprogramming has high therapeutic potential for reversing adult stem cell age, providing an advanced way to treat AADs.

[HIV infection status and related factors in men who have sex with men in sentinel surveillance in Shanxi province, 2010, 2015 and 2020].

Objective: To understand the infection status of HIV and related factors in men who have sex with men (MSM) in Shanxi province in 2010, 2015 and 2020. Methods: According to the sentinel surveillance protocol, continuous cross-sectional survey were conducted to collect the information about basic characteristics, general demographic characteristics, AIDS knowledge awareness, high-risk sexual behavior, sexually transmitted diseases, intervention services and HIV infection rate of the MSM in Shanxi in 2010, 2015 and 2020. Results: In 2010, 2015 and 2020, a total of 2 708 MSM were included in this study. There were significant differences in HIV infection rate among three years (χ2=23.76, P<0.001) with an increasing trend with year (trend χ2 =17.34, P<0.001). The rates of anal sex, commercial sex and heterosexual behavior in the past 6 months were 77.62% (2 102/2 708), 5.91% (160/2 708) and 28.14% (762/2 708) respectively, and the rates of consistent use of condom were 52.52% (1 104/2 102), 63.13% (101/160) and 23.49%(179/762) respectively, and the rate of consistent condom use was low. Results from multivariate logistic regression analysis showed that different cities, having educational level of junior high school or below, being recruited through internet, voluntary counseling and testing, suffering from sexually transmitted diseases, occasional condom use in anal sex in the past 6 months were the correlative factors of HIV infection of MSM. Conclusions: The HIV infection rate of MSM in Shanxi increased year by year from 2010, 2015 to 2020. The HIV/AIDS-related risk behavior persisted, and the proportion of condomuse adherence was low, and the HIV detection rate was low in the MSM, so targeted and effective measures should be taken to promote the condom use adherence and regular HIV testing in MSM.

[A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia].

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .