The Therapeutic Effects of Noninvasive Brain Stimulation Combined with Cognitive Training in Elders with Alzheimer's Disease or Amnesic Mild Cognitive Impairment.

BACKGROUND: Recent studies have indicated that noninvasive brain stimulation combined with cognitive interval (NIBS-CI) improved cognitive function in people with Alzheimer's disease (AD) or Amnesic mild cognitive impairment (a-MCI). While previous interventions have demonstrated that a single targeted cognitive intervention can improve cognitive function, the outcomes of using both interventions simultaneously are less well-established. Therefore, this study aims to perform a meta-analysis to determine the effectiveness of NIBS-CI in treating cognitive impairment associated with AD and a-MCI, with the goal of obtaining novel insights into this combined intervention. METHODS: PubMed, Web of Science, ProQuest and Central Cochrane library databases were searched up to December 2022. The primary cognitive outcomes were extracted from the included article. A mean difference (MD) and standardized mean difference (SMD) with a 95% confidence interval were calculated by using random-effect models. RESULTS: Twelve studies with a total of 587 AD patients were included. The findings demonstrated that NIBS-CI significantly improved cognitive function of AD patients in cognitive outcomes (SMD = -0.52, 95%CI (-0. 93, -0.11)) and ADAS-COG (MD = -1.16, 95%CI (-1.69, -0.63)). The pooled results showed that NIBS-CI did not improve cognitive function of AD patients in short-time memory (SMD = 0.057, 95%CI (-0.13, 0.25), P = 0.56) and long-time memory (SMD = 0.001, 95%CI (-0.20, 0.20), P = 0.99). CONCLUSIONS: There is evidence for a positive effect of NIBS-CI on overall cognitive function of AD and a-MCI. Considering the limited sample size, it is important to interpret the findings related to memory with caution. To obtain more robust results, future studies should be conducted with larger sample sizes and incorporate objective neurophysiological and neuroimaging tools. These methodological enhancements will allow for a better understanding of the therapeutic targets and provide a more comprehensive assessment of the effects of NIBS-CI treatment.

[Association between HBV viral load and severity of liver inflammation in patients with chronic hepatitis B virus infection].

Objective: To explore the relationship and dynamic changes between virological markers and hepatic pathological damage due to host anti-hepatitis B virus (HBV) immunity in the natural course of disease in chronic HBV infected patients. Methods: Two hundred and thirty-eight adult chronic HBV-infected patients who underwent liver biopsy from January 2016 to June 2022 in Taizhou Hospital, Zhejiang Province, were retrospectively selected. General clinical data such as age, gender, platelets, ALT, AST, albumin, HBV DNA, qHBsAg, HBeAg, and liver pathology diagnostic indexes such as the grade of liver necroinflammation and liver fibrotic stages of the patients were collected. The patients were grouped according to HBeAg status, and subgrouped according to different grades of liver necroinflammation and different HBV DNA loads. Statistical analyses were performed to compare the differences in HBV virologic marker levels between the groups, and the correlation between them and the indicators of hepatic inflammatory injury, such as ALT,AST, and the grade of liver necroinflammation in the patients. Results: The levels of HBV virological markers in HBeAg-positive patients with moderate or higher liver necroinflammatory grade (G≥2) were significantly lower than those with mild (no) liver necroinflammatory grade (G < 2) (P < 0.01); whereas the opposite trend was observed in HBeAg-negative patients, with the levels of HBV DNA, and qHBsAg in the G≥2 subgroup being significantly higher than those in the G < 2 subgroup (P < 0.01). Correspondingly, HBV DNA level and qHBsAg showed weak to moderately strong negative correlation with liver necroinflammatory grade and AST which was an indicator of hepatic inflammatory injury in HBeAg-positive patients (P < 0.05); whereas in HBeAg-negative patients, they showed weak to moderately strong positive correlation with hepatic inflammatory activity and ALT, AST (P < 0.001), in which qHBsAg showed only a weak positive correlation with patients' liver necroinflammatory grade (P = 0.003). Further subgroup analyses of HBeAg-positive patients according to whether the HBV DNA level was > 2×10(6) IU/ml showed weak to moderate negative correlations between HBV virological markers and liver necroinflammatory grade as well as ALT and AST in the subgroup of patients with HBV DNA > 2×10(6) IU/ml (P < 0.05); however, the negative correlation disappeared in patients who were still HBeAg positive and had HBV DNA ≤ 2×10(6) IU/ml. Moreover, HBV DNA and ALT, HBeAg and AST showed moderate positive correlation (P < 0.05). Conclusion: We speculate that the activation of host anti-HBV immunity can efficiently inhibit HBV replication by targeting the infected hepatocytes, but only in the early phase of disease progression in HBeAg positive patients with HBV DNA high (> 2×10(6) IU/ml).

[Correlation analysis between prenatal exposure of per-/polyfluoroalkyl compounds and neonatal outcome].

Objective: To investigate the correlation between the prenatal exposure of per-/polyfluoroalkyl substances (PFASs) and the neonatal outcome. Methods: A total of 506 maternal infant cohort samples were collected in Hangzhou, Zhejiang province from 2020 to 2021. The exposure levels of seven PFASs in maternal serum before delivery were detected by solid-phase extraction-ultra performance liquid chromatography tandem mass spectrometry. Multivariable linear regression model was used to analyze the influence of prenatal exposure of PFASs on birth weight, birth length and Apgar score. Results: The maternal age, prenatal body mass index and gestation age were (31.3±4.3) years old, (26.7±3.2) kg/m2 and (265.0±28.3) days, respectively. The birth weight, birth length and scores of Apgar-1 and Apgar-5 were (3.1±0.8) kg, (49.3±2.9) cm, (9.88±0.47) points and (9.99±0.13) points, respectively. PFASs were widely distributed in maternal serum, with the highest concentration of (18.453±19.557) ng/ml, (6.756±9.379) ng/ml and (5.057±8.555) ng/ml for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and 6∶2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA), respectively. Maternal age, parity and delivery mode were associated with the exposure level of PFASs (P<0.05). Subgroup analysis showed that PFOS had negative effects on birth weight (ß=-0.958), birth length (ß=-0.073) and Apgar-5 score (ß=-0.288) for neonates in the low birth weight (LBW) group. 6∶2 Cl-PFESA and 8∶2 Cl-PFESA inhibited the birth weight (ß=-0.926; ß=-0.552) and length (ß=-0.074; ß=-0.045) of newborn in the LBW group. In addition, 4∶2 fluorotelomer sulfonate (FTS) was associated with increased birth weight (ß=0.111) and decreased Apgar-5 score (ß=-0.030) in the normal weight group. Conclusion: Prenatal exposure to PFASs is associated with birth weight, birth length and Apgar-5 score. It is necessary to continue to pay attention to the impact of PFASs on fetal growth and development through maternal-fetal transmission.

Dentine sialophosphoprotein signal in dentineogenesis and dentine regeneration.

Dentineogenesis starts on odontoblasts, which synthesise and secrete non-collagenous proteins (NCPs) and collagen. When dentine is injured, dental pulp progenitors/mesenchymal stem cells (MSCs) can migrate to the injured area, differentiate into odontoblasts and facilitate formation of reactionary dentine. Dental pulp progenitor cell/MSC differentiation is controlled at given niches. Among dental NCPs, dentine sialophosphoprotein (DSPP) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family, whose members share common biochemical characteristics such as an Arg-Gly-Asp (RGD) motif. DSPP expression is cell- and tissue-specific and highly seen in odontoblasts and dentine. DSPP mutations cause hereditary dentine diseases. DSPP is catalysed into dentine glycoprotein (DGP)/sialoprotein (DSP) and phosphoprotein (DPP) by proteolysis. DSP is further processed towards active molecules. DPP contains an RGD motif and abundant Ser-Asp/Asp-Ser repeat regions. DPP-RGD motif binds to integrin αVß3 and activates intracellular signalling via mitogen-activated protein kinase (MAPK) and focal adhesion kinase (FAK)-ERK pathways. Unlike other SIBLING proteins, DPP lacks the RGD motif in some species. However, DPP Ser-Asp/Asp-Ser repeat regions bind to calcium-phosphate deposits and promote hydroxyapatite crystal growth and mineralisation via calmodulin-dependent protein kinase II (CaMKII) cascades. DSP lacks the RGD site but contains signal peptides. The tripeptides of the signal domains interact with cargo receptors within the endoplasmic reticulum that facilitate transport of DSPP from the endoplasmic reticulum to the extracellular matrix. Furthermore, the middle- and COOH-terminal regions of DSP bind to cellular membrane receptors, integrin ß6 and occludin, inducing cell differentiation. The present review may shed light on DSPP roles during odontogenesis.

Mitochondrial DNA Heteroplasmy of Hair Shaft Using HID Ion GeneStudioTM S5 Sequencing System.

ABSTRACT: Objective To study the heteroplasmy of the whole mitochondrial genome genotyping result of hair shaft samples using HID Ion GeneStudioTM S5 Sequencing System. Methods The buccal swabs and blood of 8 unrelated individuals, and hair shaft samples from different parts of the same individual were collected. Amplification of whole mitochondrial genome was performed using Precision ID mtDNA Whole Genome Panel. Analysis and detection of whole mitochondrial genome were carried out using the HID Ion GeneStudioTM S5 Sequencing System. Results The mitochondrial DNA sequences in temporal hair shaft samples from 2 individuals showed heteroplasmy, while whole mitochondrial genome genotyping results of buccal swabs, blood, and hair samples from the other 6 unrelated individuals were consistent. A total of 119 base variations were observed from the 8 unrelated individuals. The numbers of variable sites of the individuals were 29, 40, 38, 35, 13, 36, 40 and 35, respectively. Conclusion Sequence polymorphism can be fully understood using HID Ion GeneStudioTM S5 Sequencing system.

Serum expression of EAAT2 and ADORA2A in patients with different degrees of Alzheimer's disease.

OBJECTIVE: This study aimed to explore the correlation between serum EAAT2 and ADORA2A levels and Alzheimer's disease (AD). PATIENTS AND METHODS: A total of 68 patients with AD treated in our hospital from April 2017 to January 2019 were enrolled and assigned to group A, and 60 healthy individuals undergoing physical examinations in the same period were enrolled and assigned to group B. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of serum EAAT2 and ADORA2A in the two groups, receiver operating characteristic (ROC) curve to assess the predictive value of diagnostic efficacy, Spearman correlation to perform correlation analysis, and multivariate logistic analysis to analyze risk factors of prognosis. RESULTS: Patients from group A showed significantly higher serum ADORA2A level and lower serum EAAT2 level than individuals from group B (all p<0.001). The severity of AD was negatively correlated with the relative expression of serum EAAT2 (r=-0.7286, p<0.001), positively correlated with the relative expression of serum ADORA2A (r=0.7381, p<0.001). The sensitivity, specificity, and area under the curve (AUC) of EAAT2 alone for the diagnosis of AD were 85.00%, 82.35%, and 0.8853, respectively, and those of ADORA2A alone for the diagnosis of AD were 71.67%, 79.41.00%, and 0.8369, respectively. Univariate and multivariate Logistic regression analysis showed that disease severity, EAAT2, and ADORA2A were independent risk factors of the prognosis of AD. CONCLUSIONS: Patients with AD have highly expressed ADORA2A and lowly expressed EAAT2 in the serum. EAAT2 and ADORA2A may play parts in the progression of AD, and they can act as potential serum biomarkers for the diagnosis and disease assessment of AD.

Long noncoding RNA GAS5 enhanced by curcumin relieves poststroke depression by targeting miR-10b/BDNF in rats.

The treatment for post-stroke depression (PSD) is mainly based on a therapeutic strategy combining anti-stroke and anti-depressant drugs. In the present study, the therapeutic effect of curcumin on rats with PSD was detected by open field tests and tail suspension tests, as well as the examination of corticosterone and corticotropin-releasing hormone (CRH) levels in the serum and neurotransmitter 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and dopamine (DA) levels in the hippocampus. Curcumin notably alleviated depression compared to the controls. Furthermore, long noncoding RNA growth arrest-specific transcript 5 (GAS5) enhanced by curcumin contributed to activation of the BDNF/Trkß signaling pathway to promote the expression of synaptic-related proteins. GAS5 was demonstrated to function as a sponge of miR-10b. GAS5 upregulation by curcumin could reduce miR-10b to compromise the BDNF mRNA levels. Taken together, these results revealed a novel mechanism of curcumin on PSD through the GAS5/miR-10b/BDNF regulatory axis.

[Characteristic and clinical significance of microRNA expression between 144 Uygur and Han women with endometrial carcinoma].

OBJECTIVE: To compare the expression patterns of microRNA (miRNA) between 144 Uygur and Han women with endometrial carcinoma and to investigate their clinical significance. METHODS: Taqman miRNA low-density array was used to compare miRNA profiles between Uygur and Han women with non-endometrioid endometrial carcinoma (NEEC). Five miRNAs were further analyzed in the 144 endometrial cancers including 62 Uygur and 82 Han samples via real-time PCR to determine their expression patterns. RESULTS: MiRNA expression profiles revealed that many miRNAs overexpressed or downregula-ted in one ethnic group, but did not express or changed slightly in the other ethnic group. Further detection in the 144 endometrial cancers showed that miR-141, miR-200a, and miR-205 overexpressed in both ethnic groups. In Uygur endometrioid endometrial carcinoma (EEC), tumors with miR-141/200a overexpression tended to be more aggressive in behavior, whereas in the Han group, EEC with miR-200a overexpression was relative mild. However, the NEEC with miR-200a overexpression also had aggressive clinicopathologic features in the Han women. MiR-145 and miR-143 expressed differentially between Uygur and Han groups, they overexpressed in the former and decreased in the latter (P<0.05). In the Uygur women miR-145/143 increased significantly in NEEC and there was a trend that NEEC exhibiting favorable clinicopathologic factors had higher miR-145 expression, and was statistically significant in tumors with myometrial invasion less than 1/2 thickness (P=0.042). By contrary, miR-145/143 decreased in Han group and EEC with worse clinicopathologic variables had lower expression although without statistical significance. NEEC in Han group had no such tendency. CONCLUSION: Uygur and Han women might have different miRNA expression profiles. MiR-141/200a/205 overexpressed in endometrial carcinomas and miR-141/200a might behave differently between these two ethnic groups as well as in EEC and in NEEC. Although miR-145/143 showed inverse expression patterns between Uygur and Han women with endometrial cancer, they all exerted tumor suppression effect on endometrial cancer.

[Study on bone volume harvested from the implant sites with different methods].

OBJECTIVE: To compare the volume of autogenous bone particles harvested utilizing different techniques and various implant systems during implant surgery, and to determine the advantageous method to collect autogenous bone particles. METHODS: Homogeneous epoxy resin simulated jaw bone model was enrolled. Bicon, Bego implant systems and Straumann tissue level implant systems were utilized. The two techniques were investigated. One method was low-speed drilling (50 r/min) without water irrigating, and the other one was drilling with cold water irrigating to the ideal depth, then closing the water and drilling out with low speed (50 r/min). The bone particles in the drill groove and implant beds were collected. The volumes of the bone harvested were compared between the different techniques and also among the three implant systems, then they were compared with the volume of the bone harvested by the special bone drill. The sample size of each sub-group was 10. The bone particles were weighed by electronic balance after drying. RESULTS: The harvested bone volume between the latch reamers and hand reamers of Bicon system with the first method was not significantly different. When the same size implant bed was prepared, the volume of the bone particles produced during the implant surgery with low-speed drill without water was significantly higher than that with the other method no matter Bicon [3.5 mm×10 mm hole for example (28.42±6.04) mg vs. (6.30±2.51) mg, P<0.001] or Bego system [2.8 mm×10 mm hole for example (28.95±5.39) mg vs. (4.61±3.39) mg, P<0.001] was used, and the ratio of bone volume between the first method and the second one was approximately 3.3 to 7.0 times. When using the second method to prepare the similar size implant bed, the bone volume was not significant different among Bicon, Bego and Straumann implant systems [Bicon (9.90±3.42) mg, Bego (8.70±4.09) mg, and Straumann (10.56±5.66) mg, P=0.69]. When preparing a 5 mm-diameter-10 mm-length hole with Bicon implant system and a 4.7 mm-diameter-10 mm-length with Bego implant system, the bone quantity harvested from each group was less than that harvested by special bone drill from Neo Biotech [Bicon (82.54±12.26) mg, Bego (85.07±12.64) mg vs. Neo Biotech (96.78±13.19) mg, P<0.05]. CONCLUSION: More autogenous bone can be harvested from implant beds by preparing with low-speed rolling without water than the method with water irrigation. When utilizing the same preparing method, the implant system has no impact on the volume of the bone harvested.

Clinical practice guideline for image-guided multimode tumour ablation therapy in hepatic malignant tumours.

Multimode tumour ablation therapy is a treatment method that combines cryoablation with radiofrequency ablation, guided by medical imaging technology and based on precise planning, targeting, monitoring, and control of the thermal energy delivered, with the aim of achieving a whole-body antitumour immune response to malignant tumours. To develop standardized criteria for the application of multimode tumour ablation therapy to malignant hepatic tumours, to facilitate actualization of the criteria in various hospitals, and to ensure therapeutic efficacy and safety, the Society of Interventional Therapy of the Chinese Anti-Cancer Association and the Solid Tumor Theranostics Committee of the Shanghai Anti-Cancer Association assembled experts who specialize in oncology to discuss this treatment method and to arrive at a clinical practice consensus guideline for the indications, contraindications, and techniques of multimode tumour ablation therapy for malignant hepatic tumours.

MicroRNA-708-5p regulates mycobacterial vitality and the secretion of inflammatory factors in Mycobacterium tuberculosis-infected macrophages by targeting TLR4.

OBJECTIVE: Tuberculosis (TB), a major public health problem worldwide, is induced by Mycobacterium tuberculosis (M.tb) infection. Macrophages serve as the cellular home in immunoreaction against M.tb infection, which is tightly adjusted by host microRNAs (miRNAs) expression. The purpose of this research was to investigate the function mechanism of miR-708-5p in mycobacterial vitality and immunoreaction in human macrophages (HTP-1 and U937 cells) after M.tb infection. MATERIALS AND METHODS: Colony-forming unit (CFU) assay was used to measure mycobacterial survival. The interferon-γ (IFN-γ), interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) expression in cell supernatants were detected by enzyme-linked immunosorbent assay (ELISA). The relationship between miR-708-5p and toll-like receptor 4 (TLR4) was predicted and revealed by TargetScan and Dual-Luciferase Reporter Assay. RESULTS: Our results suggested that the miR-708-5p level was increased in a concentration-dependent and time-dependent manner in M.tb-infected human macrophages. Compared with the control group, miR-708-5p mimic enhanced the intracellular mycobacterial survival during M.tb infection, while miR-708-5p downregulation suppressed the mycobacteria survival. Moreover, the secretion of the pro-inflammatory factors, including IFN-γ, IL-6, IL-1ß, and TNF-α significantly enhanced in M.tb-induced macrophages, while miR-708-5p mimic reduced these inflammatory cytokines. Conversely, miR-708-5p inhibitor dramatically promoted the accumulation of the inflammatory factors in macrophages after M.tb treatment. In addition, evidence indicated that TLR4 was a direct and functional target of miR-708-5p. MiR-708-5p negatively regulated the TLR4 level in macrophages. CONCLUSIONS: The findings indicated that miR-708-5p level was upregulated in macrophages after M.tb infection. And miR-708-5p could regulate mycobacterial vitality and inflammatory response to M.tb infection in human macrophages by targeting TLR4.

Krüppel-like factor KLF9 inhibits chicken intramuscular preadipocyte differentiation.

1. Poultry meat quality is affected by many factors, among which intramuscular fat (IMF) is predominant. IMF content affects tenderness, juiciness and flavour of meat. Krüppel-like transcriptional factors (KLFs) are important regulators of adipocyte differentiation. However, little is known about the KLF9 gene associated with poultry IMF deposition, especially intramuscular adipocyte differentiation.2. Previous work has shown that chicken KLF9 was differentially expressed during adipogenesis of intramuscular preadipocytes differentiation. In this study, the function of KLF9 in chicken intramuscular preadipocytes differentiation was investigated.3. In the chicken preadipocyte differentiation model, KLF9 expression showed a major increase with adipogenic induction. Overexpression of KLF9 down-regulated the expression of the adipogenic marker gene AP2, and impaired triglyceride accumulation. Knockdown of KLF9 in chicken intramuscular preadipocytes increased the expression of PPARG, CEBPA and AP2. In addition, it was proposed that KLF9 may regulate adipogenesis via lncRNAs NONGGAT002209.2, NONGGAT003346.2, NONGGAT000436.2 and NONGGAT006302.2 in chicken.4. The data supported a novel role of KLF9 in regulating chicken intramuscular preadipocyte differentiation. Such findings may contribute to a more thorough understanding of chicken IMF deposition and the improvement of poultry meat quality.

[Effects of different drugs on bronchial stenosis by TGF-ß/mTOR signaling pathway in rabbit model].

Objective: To investigate the effect of different drugs on tracheal stenosis caused by transforming growth factor-ß/rapamycin target protein (TGF-ß/mTOR) signaling pathway. Methods: Thirty rabbits were randomly divided into normal control group, normal saline group, penicillin group, budesonide group and erythromycin group. The normal control group was not treated,and tracheal stenosis models were established in the other groups. From the 1st to 10th day after modeling, each group was respectively administered with normal saline (0.75 ml/kg, 2 times/d), intramuscular injection of penicillin (40 000 U/kg, 2 times/d), gastric administration of erythromycin (12.5 mg/kg, 2 times/d), inhalation of budesonide (0.05 mg/kg, 2 times/d). Rabbits were sacrificed on the 11th day after surgery, and tracheal specimens were collected to measure the degree of tracheal stenosis. Relative mRNA expression level of interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß), Type Ⅰ collagen (COL-1), Type Ⅲ collagen (COL-3), and Sirtuin 1 (SIRT-1) were detected by Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR); protein expression of mTOR, phosphorylated protein kinase B (p-AKT), vascular endothelial growth factor (VEGF),SIRT-1 were detected by immunohistochemical analysis; protein expression of nuclear factor κB (NF-κB),phosphorylated nuclear factor κB (p-NF-κB),protein kinase B (AKT),p-AKT,mTOR were detected by Western blotting. Results: The degree of stenosis of normal control group was (14.02±2.86)%, saline group was (64.14±3.21)%, penicillin group was (49.11±2.96)%, budesonide group was (39.52±2.09)%, erythromycin group was (32.60±4.27)%. The differences between any two groups were statistically significant (all P<0.05). Except between erythromycin group and normal control group, the differences in relative expression of IL-6 mRNA between any two groups (1.00±0.00, 9.02±1.50, 4.25±0.87, 2.53±0.17, 1.31±0.56) was statistically significant (all P<0.05), and the differences in relative expression of TGF-ß mRNA among all groups (1.00±0.00, 6.92±0.84, 3.83±0.44, 2.13±0.25, 1.40±0.15) were statistically significant (all P<0.05). The relative expression of SIRT-1 mRNA among all the groups (1.000±0.000, 0.209±0.042, 0.375±0.034, 0.555±0.028, 0.667±0.032) was statistically significant different (all P<0.05); except between erythromycin group and budesonide group,the protein levels of SIRT-1 among all other groups (16.93±2.28, 4.77±1.45, 7.70±0.61, 10.76±1.04, 11.03±1.10) were statistically significant different (all P<0.05). The protein levels of mTOR (9.28±4.56, 58.18±8.12, 44.75±5.56, 32.82±5.99, 24.73±3.56) and p-AKT (16.57±4.86, 61.79±6.66, 42.98±5.99, 32.79±5.34, 24.00±4.40) determined through immunohistochemistry of all groups were statistically significant different (all P<0.05). The protein levels of NF-κB, p-NF-κB, AKT, p-AKT and mTOR determined through Western blotting had the same trend as that of determined through immunohistochemistry. The protein expression of NF-κB,AKT and mTOR in saline group were significantly higher than other groups; those protein expression of erythromycin group was lower than budesonide group and penicillin group. Except between the erythromycin group and the normal control group, the protein expression of mTOR in other groups was statistically significant different (all P<0.05). Conclusion: Penicillin,erythromycin and budesonide can alleviate inflammation by increasing SIRT-1, alleviate tracheal scar hyperplasia induced by TGF-beta/mTOR pathway, and reduce the degree of tracheal stenosis in rabbits.

Assessment of the cryoablation margin using MRI-CT fusion imaging in hepatic malignancies.

AIM: To demonstrate the feasibility of magnetic resonance imaging (MRI)-computed tomography (CT) fusion imaging for the assessment of the ablative margin after cryoablation in hepatic malignancies. MATERIALS AND METHODS: This retrospective study analysed 35 patients with 47 liver tumours treated with CT-guided cryoablation. Fusion images of pre-ablation MRI and intraoperative CT data were created on a workstation. Minimal ablative margin (MAM) assessment was categorised into three groups: (I) MAM <0 mm (tumour protruded through the ablation zone), (II) MAM 0-5 mm, and (III) MAM ≥5 mm. Local tumour progression (LTP) was assessed during follow-up. RESULTS: MRI-CT fusion imaging was successfully achieved in 46 (97.9%) of 47 lesions. LTP was detected in 67.4% (31/46) of cases. Twenty-four (77.4%) of 31 LTPs occurred in the subcapsular region of the liver. Using fusion images, the MAM was classified as groups I, II, and III in 18, 25, and three tumours, respectively. In group I, LTP was found in 15 (83.3%) of 18 lesions, whereas in group II, LTP was detected in 16 (64%) of 25 lesions. The cumulative LTP rate in group II was significantly lower than that in group I (p=0.012). CONCLUSION: Pre-ablation MRI and intraoperative CT fusion imaging is feasible and useful for evaluating the MAM of cryoablation in hepatic malignancies.

Transarterial chemoembolization with raltitrexed-based or floxuridine-based chemotherapy for unresectable colorectal cancer liver metastasis.

PURPOSE: To evaluate and compare the efficiency and safety of raltitrexed- or floxuridine (FUDR)-based transarterial chemoembolization (TACE) in patients with unresectable colorectal cancer liver metastasis (CRCLM). METHODS: We conducted a retrospective analysis of 81 patients with unresectable CRCLM who failed systemic chemotherapy and were treated with TACE in our department from Oct 2014 to Oct 2017. Of these, 61 patients received TACE using raltitrexed, oxaliplatin, and pirarubicin (raltitrexed group), and 20 received TACE using FUDR, oxaliplatin, and pirarubicin (FUDR group). The objective response rate (ORR), disease control rate (DCR), overall survival (OS, from the first TACE), progression-free survival (PFS, from the first TACE), and adverse reactions were evaluated and compared between the two groups, and prognostic factors for OS were analyzed. RESULTS: The ORRs of the raltitrexed group and FUDR group were 67.2 and 45.0%, respectively (P = 0.076), and the DCRs were 86.9 and 80.0%, respectively (P = 0.452). The median OS (from first TACE) was 14.0 months in the raltitrexed group and 13.0 months in the FUDR group (P = 0.556). The median PFS (from first TACE) was 2.1 months in the raltitrexed group and 2.4 months in the FUDR group (P = 0.878). Univariate and multivariate analyses showed that the primary tumor site, Child-Pugh class, and combination with local ablation (RFA or CRA) were independent significant factors affecting survival. There were no significant differences in adverse reactions between the two groups (P > 0.05), and no treatment-related death occurred in either group. CONCLUSION: TACE treatment based on raltitrexed or FUDR is an efficient and safe alternative choice for treating unresectable CRCLM.

MiR-613 promotes cell proliferation and invasion in cervical cancer via targeting PTPN9.

OBJECTIVE: To investigate the potential effects of miR-613 on the development of cervical cancer (CC) and the relevant mechanism. PATIENTS AND METHODS: The expression level of miR-613 was detected in CC tissues and cells (siHa) by comparing with corresponding adjacent normal tissues and normal human embryonic kidney cells (293T). Luciferase assay was performed to evaluate the interaction between miR-613 and PTPN9. The effects of the miR-613 on siHa cells were determined by subsequent experiments including cell proliferation, invasion and migration. RESULTS: In our study, miR-613 was found up-regulated in CC tissues and the same result was found at cellular level. The potential target of miR-613 was analyzed by three public databases. We found that tyrosine-protein phosphatase non-receptor type 9 (PTPN9) was a direct target of miR-613, and Luciferase assays confirmed our hypothesis. The subsequent experiments showed that decreased expression of PTPN9 resulting from up-regulation of miR-613 could promote the cell proliferation, invasion and migration of CC cells. CONCLUSIONS: We showed the promotion function of miR-613 on CC by targeting PTPN9 and revealed that miR-613/PTPN9 axis might be a potential therapeutic target for the treatment of CC.

[Compare the effect of combined therapy between telbivudine plus adefovir dipivoxil and lamivudine plus adefovir dipivoxil corresponding to renal function in patients with hepatitis B virus infection].

Objective: To compare the effect of combined therapy using lamivudine (LAM) plus adefovir (ADV) versus telbivudine (LdT) plus adefovir corresponding to the renal function of CHB patients. Methods: A total of 120 patients with chronic hepatitis B were enrolled. According to single daily dosing, they were divided into 4 groups: LdT + ADV group (n = 32), ADV+LdT group (n = 28), LAM + ADV group (n = 38) and ADV + LAM group (n = 22). Hepatorenal function, HBV serological markers, HBV DNA quantification, creatine kinase (CK) and other parameters were examined every 3 months. Serum alanine aminotransferase (ALT) normalization rate, undetectable HBV DNA rate, hepatitis B e antigen (HBeAg) seroconversion rate, level of serum creatinine (CR) and estimated glomerular filtration rate (eGFR) were analyzed at baseline time, and at weeks 24 and 52.Stastical data were analyzed by t- test and analysis of variance, count data using χ (2) test. Results: There was no statistically significant difference between the four groups in terms of ALT normalization rate, HBeAg seroconversion rate, undetectable HBV DNA rate at 24 and 52 weeks. Compared with baseline, at 24 weeks of treatment, there was no significant change in serum creatinine and eGFR in the 4 groups, but after 52 weeks of treatment, serum creatinine decreased in LdT + ADV and ADV + LdT groups and eGFR increased (P < 0.05); Serum creatinine in ADV and ADV + LAM increased, and eGFR was decreased than before (P < 0.05). After treatment, there was no significant difference in renal function between the four groups at 24 weeks, but at week 52, eGFR increased and serum creatinine decreased in LdT + ADV group compared with LAM + ADV group (P < 0.05); ADV + LdT Compared with ADV + LAM group, eGFR increased and serum creatinine decreased (P < 0.05). At 52 weeks of treatment, 5 patients with mildly impaired renal function in the ADV + LdT group [n = 10, eGFR 60-90 ml·min(-1) ·(1.73 m(2))(-1)] returned to normal, and none of the ADV + LAM group (n = 9) returned to normal. Conclusion: For patients with mild impaired renal function, adding LdT combined with ADV can improve renal function compared to that of LAM plus ADV.

Systemic lupus erythematosus-associated diffuse alveolar haemorrhage: a single-centre experience in Han Chinese patients.

OBJECTIVE: Despite aggressive therapeutic regimens, diffuse alveolar haemorrhage (DAH) is still associated with a high mortality rate in systemic lupus erythematosus (SLE). This study was carried out in patients with SLE-associated DAH with a focus on their therapeutic modality. METHOD: A retrospective review was performed in 839 Han Chinese lupus patients hospitalized for their DAH manifestation from May 2006 to December 2016. RESULTS: There were 24 episodes in 17 cases (2.0% incidence), 15 females and two males aged 19-67 years (mean ± sd 38.2 ± 15.1 years). High disease activity [Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) 12-31, 19.8 ± 5.6] was found at the onset of DAH. All patients were treated with high-dose corticosteroid, followed by pulse methylprednisolone (70.6%), plasmapheresis (41.2%), pulse cyclophosphamide (35.3%), and rituximab (23.5%). Six patients (35.3%), including three with extracorporeal membrane oxygenation, died owing to acute respiratory failure. All patients receiving rituximab treatment survived with a follow-up period of 12-58 months (40.8 ± 21.1 months), and no further relapse was noted in three cases with a history of recurrent DAH episodes. In addition, there was a significant decrease in their lupus activity (SLEDAI-2K 21.5 ± 6.0 to 6.3 ± 1.7, p = 0.0286). CONCLUSION: In this single-centre series with SLE-associated DAH in Han Chinese patients, a beneficial effect of rituximab therapy was observed.