Levels, source apportionment, and risk assessment of polycyclic aromatic hydrocarbons in vegetable bases of northwest China.

Dietary consumption of contaminated vegetables is the main route of human exposure to polycyclic aromatic hydrocarbons (PAHs). However, there is a lack of research on PAHs in vegetables from northwest China. In this study, the concentrations, sources, and risk assessment of PAHs in the soil and vegetables of Urumqi, an urbanized city in Xinjiang, China, were investigated. The total concentrations of 16 PAHs in soil and vegetable samples ranged 10.58-77.20 and 93.7-1071.8 ng/g, with average values of 2.86 and 242.76 ng/g, respectively. Among vegetable samples, the concentrations were in the order: leafy vegetables (299.08 ng/g) > fruits (192.65 ng/g) > vegetable roots (152.05 ng/g). The source apportionment of PAHs was identified using positive matrix factorization. The primary sources of PAHs in soil samples are oil spills, traffic emissions, coal combustion, and coke combustion. The main sources of PAHs in vegetable samples are oil spills and burning of grass, wood, coal, and coke. In soil samples, the ecological risk caused by PAHs is at a safe level, and the incremental lifetime cancer risks (ILCRs) of ingestion exposure exceed 1.0 × 10-6, which will pose potential risks to human body. The ILCRs of vegetable samples revealed that all groups had potential risks from onion and cabbage consumption (ILCRs > 1.0 × 10-6). In particular, adult women had a higher risk of cancer (ILCRs > 1.0 × 10-4). These results emphasize the importance of combating PAHs pollution in vegetable bases.

Effects of IFN monotherapy versus combined therapy on HBeAg seroconversion or seroclearance in HBeAg-positive chronic hepatitis B patients: A meta-analysis.

BACKGROUND AND AIMS: Recent available treatment guidelines are pointing up clearance or seroconversion of hepatitis B e-antigen (HBeAg) as a valuable endpoint in treating HBeAg-positive chronic hepatitis B (CHB) patients. To evaluate the effect of combination therapy [interferon (IFN) plus nucleos(t)ide analogues (NAs)] versus IFN monotherapy on HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. METHODS: All available controlled clinical studies, published from Jan 2000 to Sep 2018, with CHB receiving IFN and NA combination therapy or IFN monotherapy were included. Risk ratio (RR) and their 95% confidence intervals (CIs) was estimated with a fixed-effects model when I2 <50% for the test for heterogeneity. Publication bias was measured using Egger's test. RESULTS: Twelve studies were included. Our meta-analysis demonstrated that IFN and NA combination therapy had a superior HBeAg seroconversion rate or clearance rate compared with IFN monotherapy at the end of treatment (EOT). Sub-analysis showed IFN plus adefovir dipivoxi (ADV) therapy had a better HBeAg seroconversion or seroclearance rate at EOT or at the end of follow-up (EOF). CONCLUSION: Compared with IFN monotherapy, the combined therapy had a higher e-antigen serological response at EOT, but failed to improve the sustained response at EOF. Only combination therapy with IFN and ADV is superior to IFN monotherapy at the EOT or EOF for HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. The effect of other combination therapies is not superior to IFN monotherapy.

Hepatitis C screening in hospitals: find the missing patients.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the leading causes of liver cancer, creating enormous economic and social burdens. The Chinese government recommends routine screening of inpatients for HCV before invasive procedures to prevent iatric infections. However, the diagnosis and treatment rates for HCV remain low. The aim of this study was to use available routine screening data to understand the HCV screening of inpatients in different regions of China. METHODS: Inpatient information and HCV screening results were collected from January 2016 to December 2016 at eight tertiary hospitals in different regions of China to compare the HCV-positivity of hospitalized patients among different regions and age groups. RESULTS: The HCV screening rate of inpatients was more than 50%. A total of 467,008 inpatients were enrolled in the study (51.20% were male), and the HCV antibody (anti-HCV) -positive rate was 0.88% (95% confidence interval [CI], 0.85-0.91%) among the total population. This rate was significantly higher among all males compared with all females (0.91% vs 0.85%). Moreover, the HCV antibody-positive rate increased with age and was highest for the 60-64-year age group. Notably, 90.14% (3722/4129) of the anti-HCV seropositive patients were 40 years of age or older. HCV screening for people over 40 years old is recommended. CONCLUSIONS: This study highlights the key role of routine examination for HCV infection in hospitalized patients. Full use of inpatient screening results to manage HCV antibody-positive patients and a screening strategy targeting inpatients 40 years and older were found to be low-cost and effective, which will help to find the missing millions of yet unaware patients and also accelerate the elimination of HCV in China.

Efficacy and Safety of Ribavirin with Sofosbuvir Plus Ledipasvir in Patients with Genotype 1 Hepatitis C: A Meta-Analysis.

BACKGROUND: Sofosbuvir and ledipasvir with or without ribavirin (RBV) regimens (SLR vs. SL) have exhibited promising results for the treatment of patients with hepatitis C virus (HCV) genotype 1 infection. AIM: To comprehensively compare the efficacy and safety of the SL and SLR regimen for the treatment of chronic HCV genotype 1 infections. METHODS: The Cochrane Library, PubMed, Web of Science, and EMBASE databases were searched. Only RCTs that compared the efficacy and safety of SL or SLR regimen for the treatment of chronic HCV genotype 1 infection were included. The primary outcome measures were the sustained virological response weeks 12 (SVR12) post-treatment and adverse events (AEs). RESULTS: Seven studies comprising 2601 patients were included. Compared with the SL regimen, SLR yielded a similar probability of having an SVR12 (RR 1.002, 95 % CI 0.998, 1.017, P = 0.780). Based on subgroup analyses, the addition of RBV to the 8-week SL regimen improved the SVR12 rate. However, the SLR regimen for 12 or 24 weeks did not show a superior SVR12 rate regardless of treatment history and the presence or absence of cirrhosis. The pooled incidence of AEs was higher in patients that received the SLR treatment regimen (RR 1.140, 95 % CI 1.095, 1.187, P = 0.000). CONCLUSIONS: The 12-week or 24-week SL regimen with a low incidence of AEs is as effective and well tolerated as the SLR regimen for the treatment of patients with chronic HCV genotype 1 infection.

Low prevalence of Neospora caninum and Toxoplasma gondii antibodies in dogs in Jilin, Henan and Anhui Provinces of the People's Republic of China.

BACKGROUND: Neospora caninum and Toxoplasma gondii are important pathogens of worldwide distribution. N. caninum is a major cause of abortion in cattle and dogs are main reservoirs because they excrete the environmentally resistant oocysts. Toxoplasmosis is a worldwide zoonosis and dogs are considered as sentinels for this parasite because of their close contact with people and cats; additionally dog meat is also used for human consumption in China. The aim of the present study was to assess the prevalence of N. caninum and T. gondii infection in dogs from China. A total of 425 countryside dog hearts in Jilin, Henan and Anhui provinces of the People's Republic of China were collected from slaughter houses in two batches; the first batch of 96 in October 2013, and the second batch of 329 in April 2014. Serum samples extracted from 96 dog hearts were tested for antibodies to N. caninum and from 425 dog hearts were tested for T. gondii antibodies in the modified agglutination tests (cut-off 1:25 for both), using respective antigens. RESULTS: Antibodies to N. caninum were 6 of 96 (6.25%) of dogs with titers of 1:25 in 2, 1:50 in 3, and 1:100 in 1. All seropositive dogs were more than 1 year old. Antibodies to T. gondii were found in 35 of 425 (8.24%) dogs with titers of 1:25 in 15, 1:50 in 14; and 1:100 in 6. CONCLUSION: The results of the present study indicated low prevalence of N. caninum and T. gondii antibodies in dogs of China, compared with Europe and America. Identification of the risk factors that underlie these differences may help prevention of neosporosis and toxoplasmosis. This is the first report of N. caninum infection in dogs from China.

Association between cognitive impairment and cardiovascular mortality in mature and older adults: A meta-analysis.

BACKGROUND: Cognitive impairment contributes significantly to negative health outcomes. This meta-analysis aimed to investigate the association between cognitive impairment and cardiovascular mortality in mature and older adults. METHODS: PubMed, Web of Science, and Embase databases were searched until February 10, 2024, to identify the association between cognitive impairment and cardiovascular mortality in mature and older adults (aged 50 years and older) from the general population. The adjusted risk estimates from the included studies were extracted and pooled using a random effects model. RESULTS: Ten studies were included in the meta-analysis, involving 16,765 participants. The pooled hazard ratio (HR) of cardiovascular mortality was 1.75 (95 % confidence interval [CI] 1.44-2.14; I2 = 48.2 %) for individuals with cognitive impairment compared to those without, even after adjusting for common confounding factors. Subgroup analysis revealed that the prognostic value of cognitive impairment may be influenced by the assessment tools used for measuring cognition. Additionally, cognitive impairment significantly predicted cardiovascular mortality in women (HR 2.40; 95 % CI 1.54-3.74; I2 = 45.4 %) but not in men (HR 1.49; 95 % CI 0.99-2.24; I2 = 44.8 %). CONCLUSIONS: Cognitive impairment is a significant predictor of cardiovascular mortality in mature and older adults from the general population. However, future studies are needed to evaluate the specific impact of cognitive impairment on different genders.

Dynamic evaluation of liver fibrosis to assess hepatocellular carcinoma risk in patients with chronic hepatitis B receiving nucleoside analogs treatment.

Despite good hepatitis B virus (HBV) inhibition by nucleoside analogs (NAs), cases of hepatocellular carcinoma (HCC) still occur. This study proposed a non-invasive predictive model to assess HCC risk in patients with chronic hepatitis B (CHB) receiving NAs treatment. Data were obtained from a hospital-based retrospective cohort registered on the Platform of Medical Data Science Academy of Chongqing Medical University, from 2013 to 2019. A total of 501 patients under NAs treatment had their FIB-4 index updated semiannually by recalculation based on laboratory values. Patients were divided into three groups based on FIB-4 index values: < 1.45, 1.45-3.25, and ≥ 3.25. Subsequently, HCC incidence was reassessed every six months using Kaplan-Meier curves based on the updated FIB-4 index. The median follow-up time of CHB patients after receiving NAs treatment was 2.5 years. HCC incidences with FIB-4 index < 1.45, 1.45-3.25, and ≥ 3.25 were 1.18%, 1.32%, and 9.09%, respectively. Dynamic assessment showed that the percentage of patients with FIB-4 index < 1.45 significantly increased semiannually (P < 0.001), and of patients with FIB-4 index ≥ 3.25 significantly decreased (P < 0.001). HCC incidence was the highest among patients with FIB-4 index ≥ 3.25. The FIB-4 index effectively predicted HCC incidence, and its dynamic assessment could be used for regular surveillance to implement early intervention and reduce HCC risk.

[Clinical observations of sequential interferon therapy following complete response to telbivudine treatment in chronic hepatitis B patients].

OBJECTIVE: To investigate the therapeutic benefit of sequential interferon alpha-1b (IFNa-1b) in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) who showed early complete response to telbivudine (LdT) treatment, and to explore the clinical value of serum hepatitis B surface antigen (HBsAg) for predicting sustained virological response (SVR). METHODS: Twenty HBeAg+ CHB patients who had shown a complete response to LdT therapy before treatment week 52 were divided into two treatment groups: one continued on the LdT treatment for an additional 6 months, and the other switched to IFNa-1b for 6 months. Each patient presented for follow-up examinations at 1, 2, 3, 6, 9, 12, 18, 24, 30 and 36 months after treatment cessation. Serum levels of alanine aminotransferase (ALT) and creatinine were detected by an automated biochemical analyzer. HBV DNA load was determined by real-time PCR. HBsAg and HBeAg levels were assessed by chemiluminescence. RESULTS: The relapse rate was lower in the group treated with sequential IFN than in the group who continued LdT treatment (30% vs. 40%, P more than 0.05). The area under the receiver operating characteristic curve at week 24 (0.689) was significantly higher than at week 12 and week 48 (0.652 vs. 0.545, P less than 0.05). Decline in serum HBsAg levels at week 24 were predictive of SVR after treatment cessation. Patients showing a decrease more than 1000 IU/ml in serum HBsAg levels at week 24 had a significantly higher SVR rate than the patients who showed a decrease less than 1000 IU/ ml (90.9%(10/11) vs. 33.3%(3/9), P less than 0.05). At the end of treatment, patients showing a decrease less than 200 IU/ml of serum HBsAg levels had a significantly higher SVR rate than those showing more than 200 IU/ml (100% vs. 53.3%, P less than 0.05). CONCLUSION: Sequential IFNa-1b consolidation therapy does not reduce the rate of relapse after treatment cessation. However, patients with a decrease in serum HBsAg levels of more than 1000 IU/ml at treatment week 24 are more likely to achieve SVR.

Latest clinical evidence about the effect of PCSK9 monoclonal antibodies in patients with familial hypercholesterolaemia: an updated meta-analysis.

INTRODUCTION: Familial hypercholesterolaemia (FH) is the most common autosomal genetic disease of cholesterol metabolism disorder. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody (mAb) is a new target lipid-regulating drug related to cholesterol metabolism that has been developed in recent years. The reported rate of reduction varies widely, and comprehensive assessments of efficacy and safety are lacking. Therefore, we conducted this study to investigate the clinical effect of PCSK9 mAbs in patients with familial hypercholesterolaemia to provide a theoretical reference for clinical practice. MATERIAL AND METHODS: We analysed the clinical data of patients, including the percentage change in LDL-C and the incidence rates of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), from selected articles. Weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated to compare the endpoints. RESULTS: The results showed that, compared with placebo, the PCSK9 mAb reduced the percentage change in LDL-C in FH patients (WMD = -45.52, 95% CI: -49.70 to -41.34, I2 = 99.6%). In addition, there was no significant difference between the experimental and placebo groups in the incidence of TEAEs (RR = 1.03, 95% CI: 0.97 to 1.10, I2 = 19.1%) and SAEs (RR = 1.02, 95% CI: 0.72 to 1.44, I2 = 0.0%). CONCLUSIONS: Overall, PSCK9 mAbs are an effective and safe method of LDL-C reduction in patients with FH.

Impact of Voltage Application on Degradation of Biorefractory Pharmaceuticals in an Anaerobic-Aerobic Coupled Upflow Bioelectrochemical Reactor.

Diclofenac, ibuprofen, and carbamazepine are frequently detected in the environment, where they pose a threat to organisms and ecosystems. We developed anaerobic-aerobic coupled upflow bioelectrochemical reactors (AO-UBERs) with different voltages, hydraulic retention times (HRTs), and types of electrode conversion, and evaluated the ability of the AO-UBERs to remove the three pharmaceuticals. This study showed that when a voltage of 0.6 V was applied, the removal rate of ibuprofen was slightly higher in the system with aerobic cathodic and anaerobic anodic chambers (60.2 ± 11.0%) with HRT of 48 h than in the control systems, and the removal efficiency reached stability faster. Diclofenac removal was 100% in the 1.2 V system with aerobic anodic and anaerobic cathodic chambers, which was greater than in the control system (65.5 ± 2.0%). The contribution of the aerobic cathodic-anodic chambers to the removal of ibuprofen and diclofenac was higher than that of the anaerobic cathodic-anodic chambers. Electrical stimulation barely facilitated the attenuation of carbamazepine. Furthermore, biodegradation-related species (Methyloversatilis, SM1A02, Sporomusa, and Terrimicrobium) were enriched in the AO-UBERs, enhancing pharmaceutical removal. The current study sheds fresh light on the interactions of bacterial populations with the removal of pharmaceuticals in a coupled system.

Comparative Analysis of the Effects of the Anti-VEGF Drug and Glucocorticoid by Injection before the End of Vitrectomy for Proliferative Diabetic Retinopathy.

OBJECTIVE: To explore the effects of the anti-VEGF drug and glucocorticoid by injection before the end of vitrectomy for proliferative diabetic retinopathy (PDR). METHODS: Eighty PDR patients who underwent vitrectomy in our hospital (July 2020-June 2022) were selected as the research objects and randomized into group A (n = 40) and group B (n = 40) according to the order of admission. Before the end of surgery, group B was injected with glucocorticoid (triamcinolone acetonide) into the vitreous cavity, and group A was injected with anti-VEGF drug (conbercept). The ophthalmic parameters, incidence of complications, diabetes indexes, and surgical indexes of the two groups were compared. RESULTS: The best corrected visual acuity (BCVA), central macular thickness (CMT), macular blood flow density and intraocular pressure in group A were remarkably better than those in group B (P < 0.001). The incidence of complications (P < 0.05) and VEG/F level (P < 0.001) in group A were obviously lower than those in group B. There was no significant difference in fasting blood glucose (FBG) and surgical indexes between the two groups (P > 0.05). CONCLUSION: Conbercept injection before the end of vitrectomy can improve the ophthalmic parameters, reduce the level of VEGF, and lower the possibility of postsurgical complications. Therefore, the low-cost and efficient anti-VEGF drug should be promoted and applied in practice.

The Effect of Brain-Computer Interface Training on Rehabilitation of Upper Limb Dysfunction After Stroke: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Upper limb motor dysfunction caused by stroke greatly affects the daily life of patients, significantly reduces their quality of life, and places serious burdens on society. As an emerging rehabilitation training method, brain-computer interface (BCI)-based training can provide closed-loop rehabilitation and is currently being applied to the restoration of upper limb function following stroke. However, because of the differences in the type of experimental clinical research, the quality of the literature varies greatly, and debate around the efficacy of BCI for the rehabilitation of upper limb dysfunction after stroke has continued. OBJECTIVE: We aimed to provide medical evidence-based support for BCI in the treatment of upper limb dysfunction after stroke by conducting a meta-analysis of relevant clinical studies. METHODS: The search terms used to retrieve related articles included "brain-computer interface," "stroke," and "upper extremity." A total of 13 randomized controlled trials involving 258 participants were retrieved from five databases (PubMed, Cochrane Library, Science Direct, MEDLINE, and Web of Science), and RevMan 5.3 was used for data analysis. RESULTS: The total effect size for BCI training on upper limb motor function of post-stroke patients was 0.56 (95% CI: 0.29-0.83). Subgroup analysis indicated that the standard mean differences of BCI training on upper limb motor function of subacute stroke patients and chronic stroke patients were 1.10 (95% CI: 0.20-2.01) and 0.51 (95% CI: 0.09-0.92), respectively (p = 0.24). CONCLUSION: Brain-computer interface training was shown to be effective in promoting upper limb motor function recovery in post-stroke patients, and the effect size was moderate.

The Impact of Steatosis on the Outcome of Liver Transplantation: A Meta-Analysis.

BACKGROUND AND AIMS: Liver transplantation is one of the most effective treatments for end-stage liver disease as well as for cases of acute liver failure. Facing organ donor shortage, liver transplant teams had to use marginal organs. Thus, increasing availability is a key concern of donor liver grafts including steatotic livers. However, the use of steatotic liver is still controversial. The aim of this systematic review and meta-analysis was to analyze the impact of steatosis on the outcome of liver transplantation. METHODS: We searched PubMed, Cochrane Library, Embase, Web of knowledge, and so on for studies published through May 31, 2018, in which patients experienced liver transplantation using fatty liver. All studies extracted outcome indicators, and we draw conclusions by contrasting outcome indicators in different groups of steatosis. Odds ratios and 95% confidence intervals were calculated. P<0.05 was considered as statistically significant difference. RESULTS: 19 publications were included. There was no significant difference between the group of no steatosis and mild group in primary nonfunction rate (P=0.605) or early graft dysfunction rate (P=0.44). The PNF rate was significantly higher in moderate group (P=0.003) and severe group (P <0.001) compared with that in no steatosis group. The same results were seen in early graft dysfunction rate. However, graft survival rate and patient survival rate did not differ between groups. CONCLUSIONS: Livers with mild steatosis, even with moderate or severe steatosis, could be suitable donor under strict control of transplant conditions.

Dynamic evaluation of liver fibrosis to assess hepatocellular carcinoma risk in patients with chronic hepatitis B receiving nucleoside analogs treatment

ABSTRACT Despite good hepatitis B virus (HBV) inhibition by nucleoside analogs (NAs), cases of hepatocellular carcinoma (HCC) still occur. This study proposed a non-invasive predictive model to assess HCC risk in patients with chronic hepatitis B (CHB) receiving NAs treatment. Data were obtained from a hospital-based retrospective cohort registered on the Platform of Medical Data Science Academy of Chongqing Medical University, from 2013 to 2019. A total of 501 patients under NAs treatment had their FIB-4 index updated semiannually by recalculation based on laboratory values. Patients were divided into three groups based on FIB-4 index values: < 1.45, 1.45-3.25, and ≥ 3.25. Subsequently, HCC incidence was reassessed every six months using Kaplan-Meier curves based on the updated FIB-4 index. The median follow-up time of CHB patients after receiving NAs treatment was 2.5 years. HCC incidences with FIB-4 index < 1.45, 1.45-3.25, and ≥ 3.25 were 1.18%, 1.32%, and 9.09%, respectively. Dynamic assessment showed that the percentage of patients with FIB-4 index < 1.45 significantly increased semiannually (P < 0.001), and of patients with FIB-4 index ≥ 3.25 significantly decreased (P < 0.001). HCC incidence was the highest among patients with FIB-4 index ≥ 3.25. The FIB-4 index effectively predicted HCC incidence, and its dynamic assessment could be used for regular surveillance to implement early intervention and reduce HCC risk.

Liver-infiltrating CD11b-CD27- NK subsets account for NK-cell dysfunction in patients with hepatocellular carcinoma and are associated with tumor progression.

Natural killer (NK) cells have a vital role in killing hepatocellular carcinoma (HCC) cells; however, the mechanism underlying tumor-infiltrating NK (TINK)-cell dysfunction remains poorly understood. Using flow cytometry staining, we precisely characterized the frequency, phenotype and function of NK subsets distinguished by CD27 and CD11b in 30 patients with HCC in comparison to 30 healthy controls. Interestingly, we found a substantial proportion of liver-infiltrating CD11b-CD27- (DN) NK subsets in tumor tissue from HCC patients. Remarkably, these relatively expanded DN NK subsets exhibited an inactive and immature phenotype. By detecting the expression of CD107a and interferon-gamma (IFN-γ) on NK subsets and NK cells, we demonstrated that DN NK subsets exhibited a poor cytotoxic capacity and deficient potential to produce IFN-γ in comparison to the other three subsets, which contributed to the dysfunction of TINK cells in HCC patients. In addition, we found that the presence of DN NK cells was closely associated with the clinical outcomes of HCC patients, as the frequency of DN NK cells among TINK cells was positively correlated with tumor stage and size. A large percentage of DN NK cells among TINK cells was an independent prognostic factor for lower survival in the 60-month follow-up period. In conclusion, a substantial proportion of CD11b-CD27-NK subsets among TINK cells accounts for NK-cell dysfunction in patients with HCC and is associated with tumor progression. Our study may provide a novel therapeutic target for the treatment of patients with HCC.

Negative regulation of tumor-infiltrating NK cell in clear cell renal cell carcinoma patients through the exosomal pathway.

Natural killer cells are the key components in tumor immunity and defects in function are necessary for tumor immune escape. Emerging studies on tumor cell-derived exosomes have shown the biological significance in tumor microenvironment, but the underlying role of exosomes in regulating natural killer cells functions in clear cell renal cell carcinoma patients remains unknown. Firstly, we precisely characterized the phenotype and function of natural killer cells in clear cell renal cell carcinoma patients vs healthy controls. With an inhibitory phenotype, tumor-infiltrating natural killer cells exhibited poor cytotoxic capacity and deficient potential to produce cytokines compared with natural killer cells from tumor margin tissue and non-tumor tissue. Next, we revealed that primary tumor cells trigged natural killer cell dysfunction in an exosome-dependent manner. Interestingly, exosomes from primary tumor cells were preferentially enriched with TGF-ß1 which acted as important mediator of natural killer cell functional deficiency. In vitro culture of exosomes induced natural killer cell dysfunction mediated by activation of the TGF-ß/SMAD signaling pathway, and abrogated by knockdown TGF-ß. Our data indicate that exosomes from clear cell renal cell carcinoma induce natural killer cells dysfunction by regulating the TGF-ß/SMAD pathway to evade innate immune surveillance.

Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats during fracture healing.

Fracture healing involves the coordinated actions of multiple cytokines. Bone morphogenetic protein 9 (BMP9) is an important factor in bone formation. The present study aimed to investigate the osteogenic potential of bone marrow stem cells (BMSCs) in response to adenoviral (Ad)BMP9, and the early fracture repair properties of AdBMP9 in surgically­created fractures in osteoporotic rats. Alkaline phosphatase (ALP) activity was assayed and matrix mineralization was examined by Alizarin Red S staining. mRNA and protein expression levels of BMP9, runt­related transcription factor 2 (RUNX2) and type 1 collagen (COL­1) were detected in vitro and in vivo. Femoral bone mineral density was assessed for osteoporosis in ovariectomized rats. An open femora fracture was subsequently created, and gelatin sponges containing AdBMP9 were implanted. The femora were harvested for radiographical, micro­computed tomography, biomechanical and histological analysis 4 weeks later. BMP9 successfully increased ALP activity and induced mineralized nodule formation in BMSCs. BMP9 in gelatin sponges demonstrated marked effects on microstructural parameters and the biomechanical strength of bone callus. In addition, it upregulated the expression levels of RUNX2 and COL­1. AdBMP9 in gelatin sponges significantly mediated callus formation, and increased bone mass and strength in osteoporotic rats with femora fractures. The results of the present study suggested that BMP9 enhanced callus formation and maintained early mechanical stability during fracture healing in osteoporotic rats, implicating it as a potential novel therapeutic target for fracture healing.

Efficacy of Tenofovir-Based Combination Therapy versus Tenofovir Monotherapy in Chronic Hepatitis B Patients Presenting with Suboptimal Responses to Pretreatment: A Meta-Analysis.

Background/Aims. It remains unclear whether tenofovir disoproxil fumarate- (TDF-) based combination therapy produces better outcomes than TDF monotherapy in chronic hepatitis B (CHB) patients. The aim of this study was to compare the efficacy of the two regimens by performing a meta-analysis. Methods. A comprehensive literature search was performed on the comparison of TDF-based combination therapy and monotherapy for CHB patients in the PubMed, Embase, Web of Science, and the Cochrane Libraries. Both dichotomous and continuous variables were extracted and pooled outcomes were expressed as risk ratio (RR) or standard mean difference (SMD). Results. Nine eligible studies (1089 subjects in total) were included in our analysis. The proportion of patients with undetectable HBV DNA at 24, 48, and 96 weeks were similar between the two comparable groups (62.5% versus 70.9%, P = 0.086; 78.1% versus 83.7%, P = 0.118; 86.4% versus 87.9%, P = 0.626, resp.). HBV DNA reduction, rates of ALT normalization, hepatitis B e antigen (HBeAg) loss, and HBeAg seroconversion were also similar between the two groups. Conclusions. On the current data, TDF-based combination therapy seemed to be no better than those achieved by monotherapy. Further studies are needed to verify this comparison.

Functional dichotomy of Vδ2 γδ T cells in chronic hepatitis C virus infections: role in cytotoxicity but not for IFN-γ production.

Vδ2 γδ (Vδ2) T cells, a major human γδ T cell subset, exhibit broad anti-tumor and anti-infective activity; however, their precise role in chronic hepatitis C virus (HCV) infections remains unclear. In this study, we analyzed the phenotype and function of Vδ2 T cells in 43 HCV-infected patients compared to 39 healthy controls (HCs). Vδ2 T cells from HCV-infected patients were activated and differentiated into effector cells. Vδ2 T cells in patients expressed significantly higher levels of natural killer (NK) cell markers CD56 and CD16 than in HCs, acquiring cytotoxic NK-like phenotype. The Vδ2 T cell phenotype was associated with increased cytolytic effector molecules expression in HCV-infected patients with elevated serum ALT levels. Surprisingly, Vδ2 T cells in patients had a markedly impaired capacity to produce IFN-γ. Further in vitro and in vivo analysis showed that interferon-α, which was induced during HCV infection, caused Vδ2 T cell function bias toward cytotoxicity. These results suggest a functional dichotomy for Vδ2 T cells in chronic HCV infections: a role in cytotoxicity but not for IFN-γ production, which may contribute to both the liver inflammation and HCV persistence.

Altered Immune Profiles of Natural Killer Cells in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Natural killer (NK) cells are the main effective component of the innate immune system that responds to chronic hepatitis B (CHB) infection. Although numerous studies have reported the immune profiles of NK cells in CHB patients, they are limited by inconsistent results. Thus, we performed a meta-analysis to characterize reliably the immune profiles of NK cells after CHB infection, specifically frequency, phenotype, and function. METHODS: A literature search of the computer databases MEDLINE, PUBMED, EMBASE, and Cochrane Center Register of Controlled Trails was performed and 19 studies were selected. The standard mean difference (SMD) and 95% confidence interval (CI) of each continuous variable was estimated with a fixed effects model when I2 < 50% for the test for heterogeneity, or the random effects model otherwise. Publication bias was evaluated using Begg's and Egger's tests. RESULTS: The meta-analysis of publications that reported frequency of peripheral NK cells showed that NK cell levels in CHB patients were significantly lower compared with that of healthy controls. A higher frequency of CD56bright NK subsets was found in CHB patients, but the CD56dim NK subsets of CHB patients and healthy controls were similar. CHB patients before and after antiviral therapy with nucleotide analogues (NUCs) showed no statistical difference in NK frequency. The activating receptors were upregulated, whereas inhibitory receptors were comparable in the peripheral NK cells of CHB individuals and healthy controls. NK cells of CHB patients displayed higher cytotoxic potency as evidenced by CD107a protein levels and conserved potency to produce interferon-gamma (IFNγ), compared with their healthy counterparts. CONCLUSION: Our results revealed that CHB patients had a lower frequency of NK cells compared with healthy individuals not treatable with antiviral NUC therapy. With an activating phenotype, NK cells in CHB patients showed better cytotoxic potency and conserved IFNγ production.