Adipokines regulate mesenchymal stem cell osteogenic differentiation.

Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies. Moreover, the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing. Recently, with the gradual recognition of adipokines, the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism, inflammation, immune regulation, energy disorders, and bone homeostasis. At the same time, the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely. Therefore, this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs, emphasizing bone formation and bone regeneration.

Early Toll-like receptor 4 inhibition improves immune dysfunction in the hippocampus after hypoxic-ischemic brain damage.

Background: Toll-like receptor 4 (TLR4) is implicated in neonatal hypoxic-ischemic brain damage (HIBD), but the underlying mechanism is unclear. Hypothesis: We hypothesized that TLR4 mediates brain damage after hypoxic ischemia (HI) by inducing abnormal neuroimmune responses, including activation of immune cells and expression disorder of immune factors, while early inhibition of TLR4 can alleviate the neuroimmune dysfunction. Method: Postnatal day 7 rats were randomized into control, HI, and HI+TAK-242 (TAK-242) groups. The HIBD model was developed using the Rice-Vannucci method (the left side was the ipsilateral side of HI). TAK-242 (0.5 mg/kg) was given to rat pups in the TAK-242 group at 30 min before modeling. Immunofluorescence, immunohistochemistry, and western blotting were used to determine the TLR4 expression; the number of Iba-1+, GFAP+, CD161+, MPO+, and CD3+ cells; ICAM-1 and C3a expression; and interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-10 expression in the hippocampal CA1 region. Result: Significantly increased TLR4 expression was observed in the left hippocampus, and was alleviated by TAK-242. The significant increases in Iba-1+, MPO+, and CD161+ cells at 24 h and 7 days after HI and in GFAP+ and CD3+ T cells at 7 days after HI were also counteracted by TAK-242, but no significant differences were observed among groups at 24 h after HI. ICAM-1 expression increased 24 h after HI, while C3a expression decreased; TAK-242 also alleviated these changes. TNF-α and IL-1ß expression increased, while IL-10 expression decreased at 24 h and 7 days after HI; TAK-242 counteracted the increased TNF-α and IL-1ß expression at 24 h and the changes in IL-1ß and IL-10 at 7 days, but induced no significant differences in IL-10 expression at 24 h and TNF-α expression at 7 days. Conclusion: Early TLR4 inhibition can alleviate hippocampal immune dysfunction after neonatal HIBD.

Features of intestinal flora in children with food protein-induced proctocolitis based on high-throughput sequencing / 中国当代儿科杂志

OBJECTIVES@#To study the features of intestinal flora in children with food protein-induced proctocolitis (FPIP) by high-throughput sequencing.@*METHODS@#A total of 31 children, aged <6 months, who experienced FPIP after exclusive breastfeeding and attended the outpatient service of the Third Affiliated Hospital of Zunyi Medical University from October 2018 to February 2021 were enrolled as the FPIP group. Thirty-one healthy infants were enrolled as the control group. Fecal samples were collected to extract DNA for PCR amplification. High-throughput sequencing was used to perform a bioinformatics analysis of 16S rDNA V3-V4 fragments in fecal samples.@*RESULTS@#The diversity analysis of intestinal flora showed that compared with the control group, the FPIP group had a lower Shannon index for diversity (P>0.05) and a significantly higher Chao index for abundance (P<0.01). At the phylum level, the intestinal flora in both groups were composed of Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes. Compared with the control group, the FPIP group had a significant reduction in the composition ratio of Actinobacteria (P<0.001) and a significant increase in the composition ratio of Proteobacteria (P<0.05). At the genus level, the intestinal flora in the FPIP group were mainly composed of Escherichia, Clostridium, Enterococcus, Klebsiella, and Bifidobacterium, and the intestinal flora in the control group were mainly composed of Bifidobacterium and Streptococcus. Compared with the control group, the FPIP group had a significant reduction in the composition ratio of Bifidobacterium and Ruminococcus (P<0.05) and significant increases in the composition ratios of Clostridium and Shigella (P<0.05).@*CONCLUSIONS@#Compared with the control group, the FPIP group has a reduction in the diversity of intestinal flora and an increase in their abundance, and there are certain differences in several bacterial genera. These results suggest that changes in the composition of intestinal flora at genus level may play an important role in the development and progression of FPIP.

Indoor and Outdoor Rodent Hosts of Orientia tsutsugamushi, Shandong Province, China.

During December 2012-July 2016, we tested small indoor and outdoor mammals in Qingdao, China, for Orientia tsutsugamushi infection. We found that outdoor Apodemus agrarius mice, Cricetulus barabensis hamsters, and Niviventer confucianus rats, as well as indoor Mus musculus mice, tested positive for O. tsutsugamushi by PCR.

Effect of thoraco-laparoscopic esophagectomy on postoperative immune function of patients with esophageal carcinoma / 南方医科大学学报

OBJECTIVE@#To investigate the effect of thoraco-laparoscopic esophagectomy on postoperative immune function of patients with esophageal carcinoma.@*METHODS@#Eighty-one patients undergoing radical esophagectomy in our hospital between January, 2017 and December, 2019 were enrolled in this study.According to the surgical approach, the patients were divided into endoscopic group (41 cases) and open surgery (3 incisions) group (40 cases).The immunological indicators (CD3@*RESULTS@#No death occurred in either of the group after the operation.On days 4 and 7 after the operation, CD3@*CONCLUSIONS@#Thoraco-laparoscopic resection of esophageal cancer can reduce postoperative secretion of proinflammatory factors, alleviate inflammatory responses, and promote the recovery of immune functions to accelerate postoperative recovery of the patients.

Value of liver/spleen stiffness combined with serum adenosine deaminase in predicting severe esophageal varices in patients with hepatitis B cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the value of liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) based on FibroTouch (FT) transient elastography combined with serum adenosine deaminase (ADA) in predicting severe esophageal varices (EV) in patients with hepatitis B cirrhosis. MethodsRelated clinical data were collected from 120 patients with hepatitis B cirrhosis who attended Department of Infectious Diseases, Changsha First Hospital, from December 2017 to June 2020. FT was used to measure LSM and SSM, and related examinations were performed, including electronic gastroscopy and serum levels of ADA, hemoglobin, albumin, alanine aminotransferase, and aspartate aminotransferase and platelet count. The serum liver fibrosis markers aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase/alanine aminotransferase ratio (AAR), and fibrosis-4 (FIB-4) were calculated. According to the severity of EV under gastroscopy, the subjects were divided into severe EV group with 58 patients and non-severe EV (without EV or with mild-to-moderate EV) group with 62 patients. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The Spearman rank correlation test was used to investigate the correlation of LSM, SSM, and ADA with severe EV. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of LSM, SSM, and ADA in the diagnosis of severe EV, and sensitivity and specificity were calculated. A multivariate binary logistic regression analysis was performed to calculate the area under the ROC curve (AUC) of the combined indicators, and the Z test was used for comparison of AUC. ResultsThere were significant differences in LSM, SSM, and ADA between the two groups (all P＜0.05). LSM, SSM, and ADA were positively correlated with severe EV, with a correlation coefficient of 0.686, 0.743, and 0.723, respectively (all P＜0.05). The optimal cut-off value was 22.35 kPa for LSM, 45.25 kPa for SSM, and 34.50 U/L for ADA in predicting severe EV, with an AUC of 0746, 0.802, and 0.791, respectively, a sensitivity of 82.8%, 75.9%, and 58.6%, respectively, and a specificity of 65.6%, 77.4%, and 90.2%, respectively. LSM+ADA, SSM+ADA, and LSM+SSM+ADA had an AUC of 0.826, 0.853, and 0.907, respectively, in predicting severe EV (all P＜0.05). ConclusionLiver/spleen stiffness combined with serum ADA has a good value in predicting severe EV, which can provide a preliminary diagnostic basis for severe EV in patients who refuse to undergo gastroscopy.

Analysis of the relationship between Clostridium genus and neonatal necrotizing enterocolitis / 公共卫生与预防医学

Objective To analyze the correlation between intestinal flora changes and neonatal necrotizing enterocolitis (NEC)through 16S rRNA metagenomic sequencing and bacterial culture. Methods From September 2018 to March 2019, 10 NEC cases and 6 controls were randomly selected in the neonatal ICU ward of Nanjing maternal and child health care hospital to analyze the 16S rRNA metagenomic diversity of the for intestinal flora. The fecal samples and corresponding environmental samples were corrected from 51 cases of NEC children and their case controls to isolate and culture Clostridium. Results The dispersion of samples within the case group was smaller than that of the control group, and the sample diversity was higher than that of the control group. In the isolation and culture of Clostridium, the overall detection rate of Clostridium in the case group was 43.14% (22/51), and the detection rate of Clostridium butyricum was the highest (19.61%, 10/51). There was a statistical difference between the two groups (χ2=5.85, P=0.015 58). All Clostridium strains did not carry the A, B and E type neurotoxin genes. Conclusion: Increased intestinal flora diversity, intestinal flora abundance and changes in the abundance of Clostridium may be closely related to the intestinal environment of children with NEC; Clostridium, especially Clostridium butyricum, may be related to the occurrence of NEC.

Genetic Structure Analysis of Y Chromosome STR and SNP in Population of Changshu / 法医学杂志

Objective To provide a theoretical basis for building a Y chromosome database in specific regions by analyzing the pedigree specific core haplogroup and region specific genetic structure in Changshu. Methods One thousand seven hundred and two samples from unrelated Han male individuals in Changshu were collected. Then 27 Y-STR were genotyped through YfilerTM Plus PCR Amplification Kit, Y-SNP haplogroup of each sample was speculated using Y-Predictor software and some samples were verified by amplification refractory mutation system-polymerase chain reaction （ARMS-PCR）. Results A total of 1 556 haplotypes were found on the 27 Y-STR genetic markers of the 1 702 samples. The haplotype diversity （HD） value was 0.999 827. DYS385 （0.933） had the highest gene diversity （GD） value while DYS438 （0.409） had the lowest. By the Y-Predictor software, all samples were confirmed to be from 162 sub-haplogroups of C, D, N, O, Q and R. Samples were randomly selected to verify the prediction results by the software and the prediction accuracy of Y-Predictor software was as high as 95.74%. Conclusion This study found that 27 Y-STR genetic markers have relatively high polymorphisms in the Changshu population, and have good forensic individual identification and paternity testing ability.

Relationship between acute kidney injury after interventional therapy and short-term prognosis in patients with acute coronary syndrome / 医学研究生学报

ObjectivePercutaneous coronary intervention (PCI) may cause acute kidney injury (AKI) in some patients with acute coronary syndrome (ACS), leading to persistent renal dysfunction. This study aimed to investigate the relationship between acute kidney injury after PCI and short-term prognosis in patients with ACS.MethodsData of 333 patients with ACS who underwent PCI in our hospital were included. According to whether the serum creatinine level was increased above 25% during 1st to 3rd day after PCI than the preoperative, patients was divided into AKI group (n=38) and non-AKI group (n=295). Risk factors for AKI in patients with ACS after PCI were analyzed. Adverse cardiovascular events and survival rates between the two groups were compared. Univariate and multivariate analysis were performed to determine the risk factors on short-term survival after surgery.ResultsAge, diabetes, preoperative renal insufficiency, left ventricular ejection fraction (LVEF), contrast dose and count of lesion coronary artery were independent risk factors for AKI after PCI (P<0.05). Within 1 year after surgery, the total incidence of cardiovascular adverse events in the AKI group and the non-AKI group were 28.9% and 5.8%, respectively, and the difference was statistically significant(χ2=20.582, P=0.000). The patients were followed up for 2.9 to 17.2 months with a median follow up of 8.6 months. The 6-month cumulative survival rate of AKI group and non-AKI group were 94.1% and 99.6%, respectively. The 1 year cumulative survival rate was 84.2% and 96.1%, respectively. The difference in overall survival rate between the two groups was statistically significant(χ2=9.216, P=0.002). Short-term survival after PCI was associated with AKI(χ2=20.582, P=0.000), LVEF (χ2=9.055, P=0.003), count of lesion coronary artery (χ2=5.749, P=0.016) and preoperative Killip grading(χ2=4.823, P=0.028). AKI and LVEF were independent predictors of short-term survival after PCI (P<0.05).ConclusionAKI in patients with ACS after PCI has a poorer short-term prognosis, which can be used as an important factor in disease assessment and risk stratification.

F-Shaped Osteotomy Combined with Basal Opening Wedge Osteotomy for Severe Hallux Valgus.

OBJECTIVE: To evaluate the safety and effectiveness of osteotomy adjacent to the articular surface of the metatarsal head combined with basal opening wedge osteotomy for severe hallux valgus. METHODS: The double osteotomy procedure was carried out in 56 patients (72 feet) with severe hallux valgus deformity, with an average follow-up of 25 months from March 2010 to February 2019. Hallux valgus angle (HVA), distal metatarsal articular angle (DMAA), intermetatarsal angle (IMA), and distal articular set angle (DASA) were measured for all patients via weight-bearing anteroposterior (AP) X-ray images. In addition, the American Orthopedic Foot & Ankle Society (AOFAS) scale was used for evaluating the function of the hallux. RESULTS: The HVA, IMA, and DMAA reduced from 49.30 ± 6.60, 19.33 ± 4.70, and 29.85 ± 10.96 to 13.19 ± 6.10, 5.97 ± 3.13, and 5.63 ± 3.44, respectively (P < 0.01). DASA decreased from 4.33 ± 2.34 to 4.08 ± 1.91 and did not show a statistically significant difference (P = 0.48). Among the 72 feet, 69 feet healed normally, and 3 feet had bone resorption at the osteotomy edges. No cases of bone sclerosis, bone necrosis, bone nonunion, or ankylosis were observed. On average, the AOFAS score improved from 34.66 ± 12.07 (preoperative) to 88.78 ± 5.73 (postoperative). CONCLUSIONS: The proposed double osteotomy procedure can maintain the match metatarsophalangeal joints without ischemic necrosis of bones, and is demonstrated to be safe, effective, and feasible for correcting severe hallux valgus.

Repression of Death Receptor-Mediated Apoptosis of Hepatocytes by Hepatitis B Virus e Antigen.

Hepatitis B virus (HBV) e antigen (HBeAg) is associated with viral persistence and pathogenesis. Resistance of HBV-infected hepatocytes to apoptosis is seen as one of the primary promotors for HBV chronicity and malignancy. Fas receptor/ligand (Fas/FasL) and the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) system plays a key role in hepatic death during HBV infection. We found that HBeAg mediates resistance of hepatocytes to FasL or TRAIL-induced apoptosis. Introduction of HBeAg into human hepatocytes rendered resistance to FasL or TRAIL cytotoxicity in a p53-dependent manner. HBeAg further inhibited the expression of p53, total Fas, membrane-bound Fas, TNF receptor superfamily member 10a, and TNF receptor superfamily member 10b at both mRNA and protein levels. In contrast, HBeAg enhanced the expression of soluble forms of Fas through facilitation of Fas alternative mRNA splicing. In a mouse model, expression of HBeAg in mice injected with recombinant adenovirus-associated virus 8 inhibited agonistic anti-Fas antibody-induced hepatic apoptosis. Xenograft tumorigenicity assay also found that HBeAg-induced carcinogenesis was resistant to the proapoptotic effect of TRAIL and chemotherapeutic drugs. These results indicate that HBeAg may prevent hepatocytes from FasL and TRAIL-induced apoptosis by regulating the expression of the proapoptotic and antiapoptotic forms of death receptors, which may contribute to the survival and persistence of infected hepatocytes during HBV infection.

PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury.

The PI3K/AKT signaling pathway is one of the most frequently activated signaling networks in human cancers and has become a valuable target in anticancer therapy. However, accumulating reports suggest that adverse effects such as severe liver injury and inflammation may accompany treatment with pan-PI3K and pan-AKT inhibitors. Our prior work has demonstrated that activation of the PI3K/AKT pathway has a protective role in Fas- or TNFα-induced hepatocytic cell death and liver injury. We postulated that PI3K or AKT inhibitors may exacerbate liver damage via the death factor-mediated hepatocyte apoptosis. In this study we found that several drugs targeting PI3K/AKT either clinically used or in clinical trials sensitized hepatocytes to agonistic anti-Fas antibody- or TNFα-induced apoptosis and significantly shortened the survival of mice in in vivo liver damage models. The PI3K or AKT inhibitors promoted Fas aggregation, inhibited the expression of cellular FLICE-inhibitory protein S and L (FLIPL/S), and enhanced procaspase-8 activation. Conversely, cotreatment with the AKT specific activator SC79 reversed these effects. Taken together, these findings suggest that PI3K or AKT inhibitors may render hepatocytes hypersensitive to Fas- or TNFα-induced apoptosis and liver injury.

Rickettsia japonica and Novel Rickettsia Species in Ticks, China.

PCR amplification indicated the minimum infection rate of Rickettsia spp. was 0.66% in Haemaphysalis longicornis ticks collected from Shandong Province, China. Phylogenetic analysis based on the rrs, gltA, ompA, and ompB genes indicated that the ticks carried R. japonica, Candidatus Rickettsia longicornii, and a novel Rickettsia species related to R. canadensis.

AKT activator SC79 protects hepatocytes from TNF-α-mediated apoptosis and alleviates d-Gal/LPS-induced liver injury.

Tumor necrosis factor-α (TNF-α) is a highly pleiotropic cytokine executing biological functions as diverse as cell proliferation, metabolic activation, inflammatory responses, and cell death. TNF-α can induce multiple mechanisms to initiate apoptosis in hepatocytes leading to the subsequent liver injury. Since the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway is known to have a protective role in death factor-mediated apoptosis, it is our hypothesis that activation of Akt may represent a therapeutic strategy to alleviate TNF-α-induced hepatocyte apoptosis and liver injury. We report here that the Akt activator SC79 protects hepatocytes from TNF-α-induced apoptosis and protects mice from d-galactosamine (d-Gal)/lipopolysaccharide (LPS)-induced TNF-α-mediated liver injury and damage. SC79 not only enhances the nuclear factor-κB (NF-κB) prosurvival signaling in response to TNF-α stimulation, but also increases the expression of cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein L and S (FLIPL/S), which consequently inhibits the activation of procaspase-8. Furthermore, pretreatment of the PI3K/Akt inhibitor LY294002 reverses all the SC79-induced hepatoprotective effects. These results strongly indicate that SC79 protects against TNF-α-induced hepatocyte apoptosis and suggests that SC79 is likely a promising therapeutic agent for ameliorating the development of liver injury. NEW & NOTEWORTHY SC79 protects hepatocytes from TNF-α-mediated apoptosis and mice from Gal/LPS-induced liver injury and damage. Cytoprotective effects of SC79 against TNF-α act through both AKT-mediated activation of NF-κB and upregulation of FLIPL/S.

The effects of hypoxia on the expression of inflammatory factor high mobility group box-1 in the pulmonary arteriolae of neonatal SD rats / 中国新生儿科杂志

Objective To study the effects of hypoxia on the expression of inflammatory factor high mobility group box-l(HMGB1) in the pulmonary arteriolae of neonatal SD rats.Method A total of 80 neonatal SD rats were randomly assigned into control group and hypoxia-induced persistent pulmonary hypertension of the newborn model (PPHN) group.The PPHN group was subdivided into 2 h,8 h,24 h,and 3 d post-PPHN subgroups according to the time of sacrifice.PPHN model was established on postnatal day 4 when rat pups in PPHN group were kept in low-oxygen box (10％ O2 and 90％ N2) for consecutively 7 days.Multi-channel physiological transducer RM-6280 was used recording the mean pulmonary artery pressure (mPAP) at the root to pulmonary artery of rat pups.ELISA method was used examining the serum level of HMGB1 of rat pups in each group.The pathology of the lung tissue was studied using optical microscope after HE staining,and MIAS-2000 medical image analysis software was used to calculate the ratio of the middle membrane thickness to the outer diameter of the pulmonary arteriolae wall (MT％).Protein level of HMGB1 in the lung was examined using Western Blot.Result The lung pathology in PPHN rats showed thickening of the middle membrane of the pulmonary arteriolae wall and stenosis of the pulmonary arteriolae.MT％ of control group and PPHN group were 5.3％ (3.7％,7.6％) and 7.1％ (4.6％,9.2％),respectively,without significant differences (P＞0.05).At 2 h,8 h,24 h,3 d post-PPHN timepoints,the serum levels of HMGB1 in PPHN group were (13.2±3.1),(15.4±3.6),(17.1±3.5),and (15.8±3.6) ng/ml,respectively,without intra-subgroup differences (F=2.134,P＞0.05),but significant differences existed when compared with control group at each timepoint (P＜0.01).Western Blot showed that HMGB1 protein expression in the lungs were significantly elevated soon after PPHN,peaked at 8～24 h,and reduced but still significantly elevated at 3 d after PPHN comparing with normal control.Significant differences existed at 2 h,8 h,and 24 h timepoints (P＜0.01,respectively).The HMGB1 protein of PPHN group declined significantly at 3 d timepoint without significant differences comparing with the control group (P＞0.05).Conclusion HMGB1 is closely related with the pathogenesis of PPHN,indicating the inflammatory response plays an important role in the mechanisms of PPHN.HMGB1 may be an indicator for the assessment of hypoxia-induced PPHN.

Genetic Structure Analysis of Y-Chromosome STR and SNP in Population of Wujiang Area, Suzhou City / 法医学杂志

Objective To analyze the genetic phenotypes of Y-chromosome STR and SNP in Han male population of Wujiang area, Suzhou City and explore the genetic structure of population of Wujiang area for further examination of regional-specific Y-SNP genetic markers ancestor haplogroups. Methods Blood samples of 472 Wujiang area Han males were randomly collected and genotyped by YfilerTM Plus PCR Amplification Kit. The allele frequencies and haplotype frequencies of each locus were obtained using the direct calculation method. Y-SNP haplogroups of each sample were estimated using Y-Predictor software and verified through experiments by amplification refractory mutation system-polymerase chain reaction （ARMS-PCR）. Results A total of 453 haplotypes were found in the 27 Y-STR genetic markers in 472 Han males of Wujiang area. The haplotype diversity （HD） was 0.997 696 93, among which, the highest gene diversity （GD） value was DYF387S1a/b （GD=0.953 1） and the lowest was DYS438 （GD=0.321 8）. Based on genotyping data of 27 Y-STRs and 472 samples, 132 haplogroups from C, D, N, O and Q, etc downstream Y-SNP haplogroups were estimated and then verified through experiments. Conclusion This study is based on Y-chromosome STR haplotypes, and predicts Y-SNP haplogroups by Y-Predictor software, then uses ARMS-PCR to verify. Y-SNP genetic markers were introduced to achieve precise analysis of the genetic structure of male families in population of three towns in Wujiang area.