The relationship and diagnostic efficacy of N-terminal propeptide type III collagen in pathological changes associated with non-alcoholic steatohepatitis.

OBJECTIVE: This study delves into the role of N-terminal propeptide type III collagen (PIIINP) in the diagnosis and management of liver pathological changes associated with non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: We collected baseline information, pathological data, and serum PIIINP levels of 168 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) via ultrasound imaging in our hospital. Based on the non-alcoholic fatty liver disease activity score (NAS), patients with different NAFLD patterns were divided into a Definite NASH group and a Not/borderline group. Differences in PIIINP levels and pathological features between the two groups were compared and analyzed. The diagnostic value of PIIINP for NASH was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Patients with NASH exhibited significantly higher values of homeostatic model assessment for insulin resistance (HOMA-IR), fibrosis biomarker fibrosis-4 (FIB-4), aminotransferase-to-platelet ratio index (APRI), and serum PIIINP levels than those classified as Not/borderline. A marked increase in the serum concentrations of PIIINP was observed with the severity of fatty degeneration, lobular inflammation, and hepatocellular ballooning. The AUC of PIIINP for diagnosing definite NASH was 0.766 (95% CI: 0.694, 0.839), APRI was 0.634 (95% CI: 0.549, 0.718), and FIB-4 was 0.621 (95% CI: 0.534, 0.708). The AUC of PIIINP for diagnosing definite NASH was significantly higher than that of APRI and FIB-4 (all p<0.05). Utilizing the predetermined threshold values for diagnostic parameters, the PIIINP measure demonstrated a sensitivity of 71.6% and a specificity of 73.6% in diagnosing definitive NASH when its value exceeded 7.72 ng/dL. This yielded a Youden index of 0.45. Similarly, when the APRI measure exceeded 0.21, it exhibited a sensitivity of 60.5% and a specificity of 63.2%, resulting in a Youden index of 0.24. Moreover, when the FIB-4 index surpassed 0.26, it showed a sensitivity of 46.9% and a specificity of 79.3%, culminating in a Youden index of 0.26. CONCLUSIONS: NASH patients in this study exhibited significantly elevated PIIINP serum levels, which were closely associated with hepatocyte pathological changes. PIIINP demonstrated superior competence in diagnosing NASH than APRI and FIB-4 and thus offers a viable alternative for the clinical diagnosis of NASH.

[Efficacy comparison of purse-string vs. linear closure of the wound following stoma reversal: systematic review and meta-analysis].

Objective: To compare the efficacy of purse-string skin closure (PSC) and linear skin closure (LSC) in stoma reversal. Methods: Randomized controlled trials (RCT) comparing the use of PSC and LSC during stoma reversal were searched from Embase, PubMed, Web of Science, CNKI net, Wanfang database, VIP Chinese Science and Technology Journal Database. Literature inclusion criteria: (1) randomized controlled trials about comparing PSC and LSC in stoma reversal published publicly; only including English literature; (2) patients undergoing stoma (ileostomy or colostomy) reversal without limitation of age, sex and ethnicity; (3) PSC group receiving the suture of the dermis layer of the skin by purse-string suture, and forming a pore channel in the center of the skin after tightening and knotting, in order to achieve the purpose of secondary healing; the LSC group receiving the suture of the skin with conventional simple interrupted suture; (4) the enrolled literatures needed to include at least one of the following outcome indicators: the primary outcome was the incidence of SSI; the secondary outcome included the operation time, incisional hernia, hospital stay and patient satisfaction. Literature exclusion criteria: (1) duplicate published studies, incomplete studies, reviews, case reports, unpublished literature, retrospective studies, non-RCT. The search time ended on November 15, 2018. The basic information and important outcome indicators of the included articles were extracted. The Cochrane bias risk assessment tool was used to evaluate the quality of the selected literatures. Patient satisfaction was assessed using the following scales: (1) the patient and observer scar assessment scale (POSAS); (2) the body image questionnaire (BIQ); (3) Likert scale; (4) short form 36 (SF-36), version 2; (5) visual analog scale (VAS). Meta-analysis was performed using Review manager 5.3 software provided by the Cochrane Collaboration. Results: A total of 9 randomized controlled trials were included, involving 806 patients with 411 cases in the PSC group and 395 cases in the LSC group. Baseline data such as age, gender, body mass index (BMI), underlying disease, and anesthesia grading were not significantly different between the two groups (all P>0.05). The quality of these nine randomized controlled trials was high. Because the evaluation methods for these studies are not uniform, it is impossible to conduct a meta-analysis of patient satisfaction. However, from the summary results of various studies, the postoperative satisfaction of the purse-string suture group was better than that of the linear suture group. The meta-analysis showed that there was significant difference in postoperative SSI incidence between the PSC group and the LSC group [OR=0.14, 95%CI: 0.08-0.24, P<0.00001], while there were no significant differences in incidence of incisional hernia [OR=0.66, 95%CI: 0.24-1.82, P=0.42], operation time [MD=0.61, 95%CI: -3.17-4.38, P=0.75], and hospital stay [MD=-0.26, 95%CI: -0.82-0.30, P=0.37]. Conclusions: PSC can be used for closure of the wound following stoma reversal. Compared with LSC, PSC can significantly reduce the incidence of SSI, and increase patients' satisfaction.

[A study regarding the control attempts on body weight and related factors among overweight and obese adults in China, 2013].

Objective: To understand the control attempts of body weight and its related factors among overweight and obese adults in China. Methods: Data was from the 2013 Chinese Chronic Diseases and Risk Factors Surveillance Program, which covered 302 surveillance sites. 179 570 adults, selected through multistage stratified cluster sampling method, were interviewed. Demographic characteristics and weight-control attempts were collected via face-to-face interview. BMI, waist circumstance and blood pressure were individually measured under physical examination. Venous blood samples were obtained and tested for FPG, OGTT-2h, TC, TG, LDL-C and HDL-C. A total of 87 545 overweight and obese patients were included in this study, with the exclusion of 152 patients having the missed critical information. Rates on weight control and attempts were analyzed, using the complex weighting on samples to represent the overall overweight and obese adults in China. Results: The rate of weight-control attempts was 16.3% (95%CI: 14.9%-17.7%). Among all the 12 133 patients who had undergone weight-control measures, the proportions of different attempts were as follows: diet (40.9%, 95%CI: 38.4%-43.3%), combination of diet and physical activity (31.5%, 95%CI: 28.9%-34.0%), physical activity (22.8%, 95%CI: 21.0%-24.6%) and drug control (1.3%, 95%CI: 1.0%-1.7%). Factors as: being female (OR=1.26, 95%CI: 1.15-1.38), at younger age (18-44 years old, OR=1.51, 95%CI: 1.31-1.74), with high education levels (college degree or above, OR=4.52, 95%CI: 3.76-5.43), having high annual income (≥24 000 Yuan, OR=1.94, 95%CI: 1.63-2.30) etc., appeared as favorable factors for taking the measures vs. rural residency (OR=0.63, 95%CI: 0.55- 0.72) as the unfavorable one. Conclusion: The rate of weight-control attempts appeared low among the overweight and obese adults who were affected by factors as age, education and income level. Personalized intervention measures should be carried out for people with different characteristics.

[Study of epidemiological characteristics of metabolic syndrome and influencing factors in elderly people in China].

Objective: To estimate the prevalence of MS in elderly people aged ≥60 years and its related factors in China and provide scientific evidence for prevention and control of MS in the elderly. Methods: Data used in this study were obtained from the 2013 Chinese Chronic Diseases and Risk Factor Surveillance Program. A total of 50 497 people aged ≥60 years were selected and interviewed through multistage stratified cluster sampling at 298 surveillance sites in 31 provinces. According to the Chinese MS diagnostic criteria proposed by the Chinese Medical Association Diabetes Branch in 2017, the prevalence rates of different MS forms were compared, and the main related factors were analyzed. Results: The prevalence rate of MS was 36.9% (95%CI: 35.4-38.5). The prevalence rate was higher in urban area than in the rural area, higher in females than in males, higher in eastern area than in western area. The prevalence rate of MS in elderly people aged ≥70 years was lower than that in those aged 60-69 years. The rate in the elderly with higher education and income levels was higher than that in the elderly with lower socioeconomic level. The comparison of the prevalence of the five forms of MS in the elderly showed that hypertension had the highest prevalence rate (72.8%), followed by hyperglycemia (41.7%) and central obesity (37.6%). The prevalence rates of hypertriglyceridemia and low HDL-C were 25.8% and 17.5%. The risk for MS in women was 1.20 times higher than that in men. Age, gender, education level, living area and urban or rural residence were the main factors influencing the prevalence of MS. Smoking, drinking and physical activity levels were correlated with MS. Conclusions: The risk for MS was higher in women than in men in China's elderly population, and the risk was related to socioeconomic level and life behaviors. It is recommended to carry out lifestyle interventions, such as increasing exercise and having reasonable diet for the elderly patients with MS. Hypertension and diabetes patients also need to be treated with drugs to reduce the risk of cardiovascular disease morbidity and mortality.

[Efficacy and security of matched unrelated donor hematopoietic stem cell transplant with transfusion of multipotent mesenchymal cells in pediatric severe aplastic anemia].

OBJECTIVE: To observe the efficacy of matched unrelated donor hematopoietic stem cell transplant (HSCT) with transfusion of multipotent mesenchymal cells (MSC) in pediatric severe aplastic anemia (SAA). METHODS: 19 children with SAA received matched unrelated donor HSCT with MSC, and the hematopoietic recovery and transplant-associated complications of these children were monitored. RESULTS: All patients achieved rapid hematopoietic reconstruction after HSCT, and the median durations to neutrophil and platelet recovery were 12 (9-21) days and 14 (8-24) days respectively, but delayed rejection occurred in one case four months after HSCT. 9 cases developed grade Ⅰ acute graft-versus-host (aGVHD), and one case grade Ⅲ aGVHD and diffuse chronic graft-versus-host. Cytomegalovirus viremias were observed in 15 patients. 2 cases developed hemorrhagic cystitis, 10 children experienced infections. All the children were alive during a median following-up time of 27(8-70) months, one of them developed LPD and received rituximab and chemotherapy, delayed rejection occurred in this patient four months after HSCT, Haplo-identical HSCT from his father as the donor was performed and achieved successful engraftment. CONCLUSION: The matched unrelated donor HSCT with MSC in pediatric SAA was safe and effective.

I148M variant of PNPLA3 increases the susceptibility to non-alcoholic fatty liver disease caused by obesity and metabolic disorders.

BACKGROUND: The patatin-like phospholipase 3 (PNPLA3) rs738409 gene polymorphism is an important genetic determinant of non-alcoholic fatty liver disease (NAFLD). However, the associations between liver fat and metabolic traits in rs738409 G allele carriers and the allelic influence on this association have not been fully studied. AIM: To investigate the influence of the PNPLA3 gene polymorphism on the association of liver fat with serum metabolic factors and carotid atherosclerosis. METHODS: Liver fat was measured by quantitative ultrasound in 4300 subjects in the Shanghai Changfeng community and analysed for its association with obesity and metabolic factors in individuals with the PNPLA3 CC, CG and GG genotypes. RESULTS: Non-alcoholic fatty liver disease occurred in 37.9% and 28.8% of the subjects with the GG and CC genotypes respectively (P < 0.001). Liver fat was significantly associated with body mass index, waist circumference, serum triglycerides, high-density lipoprotein cholesterol, fasting blood glucose and insulin in the PNPLA3 rs738409 G allele carriers (P < 0.001). Compared with the CC homozygotes, the GG homozygotes presented higher liver fat and liver fibrosis scores despite their better metabolic status (comparison of regression line slopes, P < 0.05). An increase in liver fat was accompanied by a significant increase in the average and maximum carotid intima-media thickness in subjects with the PNPLA3 CC genotype but not in those with the GG genotype. CONCLUSIONS: PNPLA3 rs738409 G allele carriers were found to be more susceptible to the metabolic-related hepatic steatosis, and developed NAFLD and liver fibrosis despite presenting relatively better metabolic statuses and lower risks for carotid atherosclerosis.

Flagellin-PAc Fusion Protein Inhibits Progression of Established Caries.

Dental caries remains one of the most common infectious diseases of humankind, which develops slowly throughout life, affecting children, adolescents, and adults. A vaccine against caries is urgently needed. We previously developed recombinant flagellin as a mucosal adjuvant for anti-Streptococcus mutans vaccines by nasal immunization. Furthermore, we demonstrated a fusion protein strategy that combined flagellin and the target surface adhesion protein (PAc) in a single construct. This construct enhanced specific IgA responses in oral fluids and provided improved prophylactic protection against caries. In the present study, we observed prolonged progression of dental caries in rats after S. mutans Ingbritt challenge. In addition, we observed a therapeutic effect of the flagellin-PAc fusion protein (KF-rPAc) against dental caries as a mucosal vaccine with a new immunization protocol. The present study demonstrated that KF-rPAc by nasal immunization can promote PAc-specific systemic and mucosal antibody responses and inhibit dental caries progression efficiently after the implant of S. mutans into the oral cavity of the rats. The rats immunized with KF-rPAc exhibited 53.9% caries reduction compared with the sham-immunized rats. Our data support the concept of administration of KF-rPAc to humans after infection and even caries that has begun to alleviate caries progression. In conclusion, our study demonstrated that KF-rPAc could be used as an anticaries therapeutic mucosal vaccine.

Gpr97 is essential for the follicular versus marginal zone B-lymphocyte fate decision.

Gpr97 is an orphan adhesion GPCR and is highly conserved among species. Up to now, its physiological function remains largely unknown. Here, we show that Gpr97 deficiency results in an extensive reduction in B220(+) lymphocytes in mice. More intensive analyses reveal an expanded marginal zone but a decreased follicular B-cell population in Gpr97(-/-)spleen, which displays disorganized architecture characterized by diffuse, irregular B-cell areas and the absence of discrete perifollicular marginal and mantle zones. In vivo functional studies reveal that the mutant mice could generate antibody responses to T cell-dependent and independent antigens, albeit enhanced response to the former and weakened response to the latter. By screening for the molecular events involved in the observed phenotypes, we found that lambda 5 expression is downregulated and its upstream inhibitor Aiolos is increased in the spleen of mutant mice, accompanied by significantly enhanced phosphorylation and nuclear translocation of cAMP response element-binding protein. Interestingly, increased constitutive Nf-κb p50/p65 expression and activity were observed in Gpr97(-/-) spleen, implicating a crucial role of Gpr97 in regulating Nf-κb activity. These findings uncover a novel biological function of Gpr97 in regulating B-cell development, implying Gpr97 as a potential therapeutic target for treatment of immunological disorders.

Flagellin-PAc fusion protein is a high-efficacy anti-caries mucosal vaccine.

We previously demonstrated that an anti-caries DNA vaccine intranasally administered with recombinant flagellin protein as a mucosal adjuvant enhanced salivary IgA response and conferred better protection against caries. However, the relatively weak immunogenicity of DNA vaccines and the necessity for a large quantity of antigens remain significant challenges. Here, we fused the flagellin derived from E. coli (KF) and target antigen PAc containing the A-P fragment of PAc from S. mutans (rPAc) to produce a single recombinant protein (KF-rPAc). The abilities of KF-rPAc to induce rPAc-specific mucosal and systemic responses and protective efficiency against caries following intranasal immunization were compared with those of rPAc alone or a mixture of rPAc and KF (KF + rPAc) in rats. Results showed that KF-rPAc promoted significantly higher rPAc-specific antibodies in serum as well as in saliva than did an equivalent dose of rPAc alone or a mixture of KF + rPAc. Intranasal immunization of 8.5 µg KF-rPAc could achieve 64.2% reduction of dental caries in rats. In conclusion, our study demonstrated that flagellin and PAc fusion strategy is promising for anti-caries vaccine development, and KF-rPAc could be used as an anti-caries mucosal vaccine.

Flagellin enhances saliva IgA response and protection of anti-caries DNA vaccine.

We and others have shown that anti-caries DNA vaccines, including pGJA-P/VAX, are promising for preventing dental caries. However, challenges remain because of the low immunogenicity of DNA vaccines. In this study, we used recombinant flagellin protein derived from Salmonella (FliC) as a mucosal adjuvant for anti-caries DNA vaccine (pGJA-P/VAX) and analyzed the effects of FliC protein on the serum PAc-specific IgG and saliva PAc-specific IgA antibody responses, the colonization of Streptococcus mutans (S. mutans) on rat teeth, and the formation of caries lesions. Our results showed that FliC promoted the production of PAc-specific IgG in serum and secretory IgA (S-IgA) in saliva of rats by intranasal immunization with pGJA-P/VAX plus FliC. Furthermore, we found that enhanced PAc-specific IgA responses in saliva were associated with the inhibition of S. mutans colonization of tooth surfaces and endowed better protection with significant fewer caries lesions. In conclusion, our study demonstrates that recombinant FliC could enhance specific IgA responses in saliva and protective ability of pGJA-P/VAX, providing an effective mucosal adjuvant candidate for intranasal immunization of an anti-caries DNA vaccine.

GPR26-deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala.

Anxiety disorders are among the most common and well studied psychiatric disorders in humans. A number of animal models have been established to study the mechanisms of anxiety and to test putative anxiolytic drugs. Gpr26 belongs to the G-protein-coupled receptor family and is exclusively expressed in brain tissue. To investigate the biological function of Gpr26 in vivo, we have generated Gpr26 knockout mice. The mutant mice grew and developed normally but displayed increased levels of anxiety-like behaviors in the open field and elevated plus maze tests, as well as a higher level of depression-like behaviors in the forced-swim and tail-suspension tests. Meanwhile, no significant alteration in spatial learning and memory abilities were found for Gpr26-deficient mice in the Morris water maze test. Previous studies demonstrated that lower protein kinase A (PKA)-cAMP responsive element-binding protein (CREB)-neuropeptide Y (NPY) signaling in the amygdala is linked to higher anxiety and excessive alcohol-drinking behaviors in rats. Therefore, we further examined the phosphorylated CREB (pCREB) and CREB levels in the brains of Gpr26-deficient mice. Reduced pCREB levels were observed in the central amygdala but not in the other regions, while total CREB levels remained comparable between wild-type and mutant mice. Combined, our data indicate that Gpr26 is important for emotion regulation in mice, a function probably mediated by the phosphorylation of CREB in the central amygdala.

Anti-CD25 monoclonal antibody (basiliximab) for prevention of graft-versus-host disease after haploidentical bone marrow transplantation for hematological malignancies.

Haploidentical donors are available for most patients who need allografts but do not have matched donors. However, GVHD, rejection, delayed immune reconstitution, and infections have been significant barriers. We designed a haploidentical BMT protocol focusing on prevention of GVHD and rejection. A total of 53 leukemic patients underwent haploidentical G-CSF-primed BMT without ex vivo T-cell depletion. GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine, methotrexate, and mycophenolate mofetil. In all, 38 patients (the CD25 group) received additional anti-CD25 monoclonal antibody basiliximab. The results were compared to 15 patients who did not receive basiliximab. All patients achieved trilineage engraftment with full-donor chimerism. The incidence of acute II-IV GVHD was 11% in the CD25 group vs 33% in the control group (P=0.046). The overall incidence of extensive chronic GVHD was 15%. T, B, and NK cells recovered within 12 months post transplant. The disease-free survival at 2 years was 53% with a median follow-up of 31 months. In conclusion, G-CSF primed haploidentical BMT along with sequential immunosuppressive agents as described here deserves further study.

G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia.

Based on our encouraging results of G-CSF-primed HLA-matched related marrow transplants for high-risk leukemia, we extended the study from matched related to haploidentical transplants using G-CSF primed marrow and sequential immunosuppressants to prevent both graft-versus-host disease (GVHD) and host-versus-graft rejection (HVGR). Fifteen high-risk leukemia patients, who needed urgent transplantation but lacked an HLA-matched donor, underwent G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion. Donors were given G-CSF (Lenograstim) at 3-4 microg/kg/day for 7 days prior to marrow harvest. GVHD and HVGR prophylaxis were combined in the sequential usage of cyclosporin A, methotrexate, anti-thymocyte globulin and mycophenolate mofetil. All patients established sustained trilineage engraftment at a median of 19 days and 21 days for neutrophil and platelets respectively. G-CSF priming significantly increased CD34(+) and CFU-GM cells, reduced total lymphocytes and reversed the CD4(+)/CD8(+) ratio in the donor marrow. The incidence of grade II-IV acute GVHD was 33.3%. Nine patients survived more than a year with a Karnofsky performance status of 100%. Estimated overall disease-free survival at 2 years was 60 +/- 7%. In conclusion, using G-CSF priming marrow grafts along with sequential immunosuppressants provided an excellent alternative for the treatment of high-risk hematological malignancy in patients who lack matched donors.