Diagnostic value of dynamic contrast enhancement combined with conventional MRI in differentiating benign and malignant lacrimal gland epithelial tumours.

AIM: To establish the diagnostic value of the quantitative parameters of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) combined with conventional MRI in differentiating of benign and malignant lacrimal gland epithelial tumours. MATERIALS AND METHODS: A retrospective analysis of primary lacrimal gland epithelial tumours confirmed by histopathology was conducted. Conventional MRI features and DCE-MRI quantitative parameters were collected and subjected to analysis. The diagnostic value was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 53 patients were enrolled of which 29 had malignant, whereas 24 had benign tumours. Conventional MRI revealed statistically significant differences between benign and malignant tumours regarding maximum tumour diameter, posterior margin characteristic, bone destruction, and erosion. The Ktrans and Kep values obtained by DCE-MRI were higher in malignant than in benign tumours, with a statistically significant (p<0.001 and p=0.022). A type I time-signal intensity (TIC) curve was more frequent in benign tumours, whereas a type II TIC curve was prevalent in malignant tumours (p=0.001). ROC analysis showed that Ktrans had the best diagnostic value of the DCE-MRI parameters (area under the ROC curve [AUC] of 0.822, 75.9% sensitivity, and 83.3% specificity, p<0.001). The combination of conventional MRI and DCE-MRI factors had the best diagnostic value and balanced sensitivity and specificity (AUC of 0.948, 93.1% sensitivity, and 91.7% specificity, p<0.001). CONCLUSIONS: The present findings indicate that the combination of quantitative parameters of DCE-MRI and image characteristics of conventional MRI have a high diagnostic value for the diagnosis of benign and malignant lacrimal gland epithelial tumours.

Effect of rumen-protected choline on dairy cow metabolism, immunity, lactation performance, and vaginal discharge microbiome.

Rumen-protected choline (RPC) promotes benefits in milk production, immunity, and health in dairy cows by optimizing lipid metabolism during transition period management and early lactation. However, the RPC success in dairy cows depends on choline bioavailability, which is affected by the type of protection used in rumen-protected choline. Therefore, our objectives were to determine the effects of a novel RPC on dry matter intake (DMI), identify markers of metabolism and immunity, and evaluate lactation performance. Dry Holstein (n = 48) cows at 245 ± 3 d of gestation were blocked by parity and assigned to control or RPC treatment within each block. Cows enrolled in the RPC treatment received 15 g/d of CholiGEM (Kemin Industries, Cavriago RE, Italy) from 21 d prepartum and 30 g/d of CholiGEM from calving to 21 d postpartum. During the transition period, DMI was measured daily, and blood was sampled weekly for energy-related metabolites such as ß-hydroxybutyrate (BHB), glucose, and nonesterified fatty acids (NEFA), as well as immune function markers such as haptoglobin (Hp) and lipopolysaccharide-binding protein (LPB). Vaginal discharge samples were collected at the calving and 7 d postpartum and stored in microcentrifuge tubes at -80°C until 16S rRNA sequencing. The main responses of body condition score, body weight, DMI, milk yield, milk components, and immune function markers were analyzed using the GLIMMIX procedure of SAS with the effects of treatment, time, parity, and relevant covariates added to the models. The relative abundance of microbiome α-diversity was evaluated by 3 indexes (Chao1, Shannon, and Simpson) and ß-diversity by principal coordinate analysis and permutational multivariate ANOVA. We found no differences in DMI in the pre- and postpartum periods. Cows fed RPC increased the yields of energy- and 3.5% fat-corrected milk and fat yield in primiparous and multiparous cows, with an interaction between treatment and parity for these lactation variables. However, we found no differences in milk protein and lactose up to 150 DIM between treatments. Glucose, NEFA, and BHB had no differences between the treatments. However, RPC decreased BHB numerically (control = 1.07 ± 0.13 vs. RPC = 0.63 ± 0.13) in multiparous on the third week postpartum and tended to reduce the incidence of subclinical ketosis (12.7% vs. 4.2%). No effects for Hp and LPB were found in cows fed RPC. Chao1, Shannon, and Simpson indexes were lower at calving in the RPC treatment than in the Control. However, no differences were found 7 d later for Chao1, Shannon, and Simpson indexes. The vaginal discharge microbiome was altered in cows fed RPC at 7 d postpartum. Fusobacterium, a common pathogen associated with metritis, was reduced in cows fed RPC. Rumen-protected choline enhanced lactation performance and health and altered the vaginal discharge microbiome which is a potential proxy for uterine healthy in dairy cows. The current study's findings corroborate that RPC is a tool to support adaptation to lactation and shed light on opportunities for further research in reproductive health.

[circDDX17 targets miR-223-3p / RIP3 to regulate the proliferation and apoptosis of non-small cell lung cancer cells].

Objective: To explore the molecular mechanism of circDDX17 regulating the proliferation and apoptosis of non-small cell lung cancer cells by targeting the miR-223-3p/RIP3 molecular axis. Methods: The expression levels of circDDX17, miR-223-3p, and RIP3 in human normal lung epithelial cell lines BEAS-2B and non-small cell lung cancer cells H1299, A549, and H446 were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The plasmids of pcDNA, pcDNA-circDDX17, anti-miR-con, anti-miR-223-3p, pcDNA-circDDX17 and miR-con, pcDNA-circDDX17 and miR-223-3p mimics were transfected into H1299 cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was used to detect the cell proliferation. Flow cytometry was used to detect the cell cycle and cell apoptosis. Plate cloning experiment was used to detect cell proliferation ability. The dual luciferase report experiment was applied to verify the targeting relationship between miR-223-3p with circDDX17 and RIP3. Western blot was used to detect the protein expression of cyclinD1, CDK2, cleaved caspase-3 and Bax. Results: The expression levels of circDDX17 and RIP3 mRNA in H1299, A549, and H446 cells were significantly reduced (P<0.05), the expression level of miR-223-3p mRNA was significantly increased (P<0.05) compared with BEAS-2B. The cell viability [(69.46±4.68)%], the number of cell clones (83.49±7.86), the proportion of cells in S phase [(22.52±1.41) %], the protein expression levels of cyclinD1 and CDK2 in PCDNa-CircDDX17 group were lower than those in pcDNA group [(97.54±7.72)%, 205.03±13.37, (28.69±1.49)%, respectively, P<0.05], while the percentage of G0/G1 phase cells [(64.45±3.56)%], apoptosis rate [(18.36±1.63)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17 group were higher than those of pcDNA group [(51.33±2.76) % and (5.21±0.54) %, respectively, P<0.05]. The viability [(72.64±5.44)%], the number of cell clones (78.16±8.23), the proportion of S-stage cells [(21.34±1.59) %], the protein expression levels of CyclinD1 and CDK2 in anti-miR-223-3p group were lower than those in anti-miR-con group [(103.47±6.25)%, 169.32±14.53, (28.43±1.26)%, respectively, P<0.05]. Percentage of G0/G1 phase cells [(62.86±3.28)%], apoptosis rate [(14.64±1.67)%], the protein expression levels of cleaved caspase-3 and Bax in the anti-miR-223-3p group were higher than those of anti-miR-con group [(51.33±2.71)% and (4.83±0.39)%, respectively, P<0.05]. MiR-223-3p has complementary sites with circDDX17 or RIP3. The viability [(135.45±9.28)%], the number of cell clones (174.64±10.68), the proportion of S-phase cells [(26.39±2.25)%], the protein expression levels of cyclinD1 and CDK2 in pcDNA-circDDX17+miR-223-3p group were higher than those in pcDNA-circDDX17+miR-con group [(101.56±6.68)%, 107.65±7.62, (21.64±1.72)%, P<0.05]. Percentage of G0/G1 phase cells [(56.64±2.76)%], apoptosis rate [(8.34±0.76)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17+miR-223-3p group were lower than those of pcDNA-circDDX17+miR-con group [(64.03±3.48)% and (15.21±1.18)%, respectively, P<0.05]. Conclusion: circDDX17 could inhibit the proliferation and induce apoptosis of non-small cell lung cancer cells via targeting the miR-223-3p / RIP3 molecular axis.

[Efficacy of rituximab therapy for 10 patients suffering from systemic lupus erythematosus with intestinal involvement].

We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.

[Transperineal targeted prostate puncture combined with rapid pathological examination in the diagnosis of prostate cancer].

Exploring the clinical value of multiparametric magnetic resonance (Mp-MRI)-cognitive fusion method of targeted transperineal prostate puncture combined with rapid pathological diagnosis. Patients with suspected prostate cancer admitted to our hospital from 2022.01 to 2023.05 were selected as the study subjects, and Mp-MRI was performed and the suspected lesions were scored by the Prostate Imaging Reporting and Data System (PI-RADS). The enrolled patients were randomly divided into the transperineal prostate targeted puncture plus rapid pathology group (experimental group) and the transperineal prostate systematic combined targeted puncture plus conventional pathology group (control group), and the positive puncture rate, pathological findings, and complications were analyzed to compare the differences between the two groups. A total of 100 patients were enrolled, 53 in the experimental group [age 55-89 years, (73.17±7.79) years; tPSA 7.01-100 µg/L, mean 21.34 (12.38, 44.42) µg/L]and 47 in the control group [age 60-87 years, (71.96±7.07) years; tPSA 6.11-98.82 µg/L, mean 18.77 (9.04, 38.09) µg/L], and there was no significant difference between the two groups in the diagnostic positivity rate of overall PCa and clinically significant PCa (P>0.05); there was no significant difference in the highest Gleason score of pathological tissues between the two groups (P>0.05); the number of cases of medically induced sarcoid hematuria in the experimental group were significantly reduced compared with the control group (P<0.05). In terms of biopsy pain score (VAS), patients in the experimental group experienced less pain than those in the control group (P<0.05). The Mp-MRI-cognitive fusion method of transperineal targeted prostate puncture combined with rapid frozen section pathological examination can provide rapid and accurate pathological results, reduce the chance of post-puncture complications, and alleviate the pain caused by puncture sampling, which has high clinical value.

Does gestational diabetes mellitus increase the risk of cardiovascular disease? A Mendelian randomization study.

PURPOSE: In recent years, epidemiological studies have revealed the relationship between gestational diabetes mellitus (GDM) and cardiovascular disease (CVD). In this study, we utilized Mendelian randomization (MR) to investigate the potential causal impact of GDM on cardiovascular disease for the first time. METHODS:  We retrieved summary statistics from published genome-wide association studies. MR was first performed using significant SNPs extracted from the eighth data release of the FinnGen study. Next, a replication analysis for coronary artery disease (CAD) was conducted in another European ancestry population to validate our findings. Finally, mediation analysis was carried out to assess potential mediation effects. RESULTS: Our data analysis revealed that genetically predicted GDM was significantly associated with increased CAD risk (OR 1.10, 95% CI 1.02-1.18, p 0.006). Replication analysis confirmed a significant genetic association between GDM and CAD (OR 1.07, 95% CI 1.02-1.12, p 0.003) in another European ancestry population. Mediation analysis indicated no significant mediation effect by type 2 diabetes mellitus (T2DM) on the GDM-CAD relationship (mediation effect ß [95% CI]: 0.005 [-0.003, -0.017]). CONCLUSION: Women with a prior history of GDM face an elevated risk of future CAD. This increased risk of CAD cannot be solely attributed to the subsequent onset of diabetes. Regular CAD risk assessment and primary prevention strategies are of paramount importance for women with a history of GDM.

[The expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells].

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and ß-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

[Comparison of clinical effects between periodontal endoscopy aiding subgingival debridement and flap surgery].

OBJECTIVE: To compare the clinical effects of periodontal endoscopy aiding subgingival debridement with periodontal flap surgery on residual deep pockets of chronic periodontitis. METHODS: In the single-blind randomized control clinical study, residual deep pockets of periodontitis patients were still existing when re-evaluation after receiving initial periodontal treatment.The pockets which were necessary for bone surgery or guided tissue regeneration surgery were excluded.The sites were divided into test group and control group randomly.Test group sites underwent periodontal endoscopy aiding debridement and control group sites had periodontal flap surgery.At the baseline and 3 months later, parameters, such as plaque index (PLI), bleeding index (BI), probing depth (PD), attachment loss (AL) were examined.Bone height was measured by parallelly digital X-ray dental film.Meanwhile, treatment time and comfort scale (visual analogue scale, VAS) were also recorded. RESULTS: At baseline, 41 proximal sites with residual deep pockets were enrolled (test sites=21, control sites=20).All the parameters were not significantly different between the two groups.PD decreased by (1.67±0.91) mm from (5.62±0.86) mm to (3.95±0.74) mm in test group and by (2.25±1.12) mm from (5.95±1.19) mm to (3.70±0.73) mm in control group significantly (P < 0.05).The difference between the two groups was not significant.The PD of all the sites decreased lower than 5 mm, meanwhile, 76% was lower than 4 mm in test group and 85% was lower than 4 mm in control group.The BI decreased by 0.81±0.93 in test group and 0.65±0.99 in control group significantly (P < 0.05).The difference between the two groups was not significant.The PLI showed a tendency of decrease more in test group and bone height showed a trend of decrease more in control group, however, the difference was not significant.The treatment time was almost the same.The patients felt more comfortable in the test group (VAS was 0.60±0.89) than the control group (VAS was 1.20±1.64), however, the difference was not significant. CONCLUSION: Periodontal endoscopy aiding subgingival debridement could improve periodontal status by reducing the PD and BI significantly in short term.The effect was almost the same with periodontal surgery and endoscopy treatment may decrease the necessity of surgery.Meanwhile, periodontal endoscopy has more comfortable treatment experience than flap surgery and does not need extra treatment time.

[Profiles and differences of submucosal microbial in peri-implantitis and health implants: A cross-sectional study].

OBJECTIVE: To describe the submucosal microbial profiles of peri-implantitis and healthy implants, and to explore bacteria that might be correlated with clinical parameters. METHODS: In the present cross-sectional study, 49 patients were recruited. Each patient contributed with one implant, submucosal biofilms were collected from 20 healthy implants and 29 implants with peri-implantitis. DNA was extracted and bacterial 16S ribosomal RNA (16S rRNA) genes were amplified. Submucosal biofilms were analyzed using 16S rRNA sequencing at Illumina MiSeq platform. Differences between the groups were determined by analyzing α diversity, microbial component and microbial structure. The potential correlation between the bacteria with pocket probing depth (PPD) of peri-implant calculated by Spearman correlation analysis. RESULTS: The α diversity of submucosal microbial of health group was significantly lower than that in peri-implantitis group (Chao1 index: 236.85±66.13 vs. 150.54±57.43, P < 0.001; Shannon index: 3.42±0.48 vs. 3.02±0.65, P=0.032). Principal coordinated analysis showed that the submucosal microbial structure had significant difference between healthy and peri-implantitis groups [R2=0.243, P=0.001, analysis of similarities (ANOSIM)]. Compared with healthy implants, relative abundance of periodontal pathogens were higher in peri-implantitis, including members of the red complex (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and some members of orange complex (Precotella intermedia, Eubacterium nodatum, Parvimonas micra), as well as some new periodontal pathogens, such as Fillifactor alocis, Fretibacterium fastidiosum, Desulfobulbus sp._HMT_041, and Porphyromonas endodontalis. Spearman correlation analysis revealed that the relative abundance of Treponema denticola (r=0.686, P < 0.001), Tannerella forsythia (r=0.675, P < 0.001), Fretibacterium sp. (r=0.671, P < 0.001), Desulfobulbus sp._HMT_041 (r=0.664, P < 0.001), Filifactor alocis (r=0.642, P < 0.001), Fretibacterium fastidiosum (r=0.604, P < 0.001), Porphyromonas gingivalis (r=0.597, P < 0.001), Porphyromonas endodontalis (r=0.573, P < 0.001) were positive correlated with PPD. While the relative abundance of Rothia aeria (r=-0.615, P < 0.001) showed negatively correlation with PPD. CONCLUSION: Marked differences were observed in the microbial profiles of healthy implants and peri-implantitis. The members of red and orange complex as well as some new periodontal pathogens seem to play an important role in peri-implant disease. Compared with healthy implants, the submucosal microbial of peri-implantitis were characterized by high species richness and diversity.

[Effects of surface treatment on the phase and fracture strength of yttria- and magnesia-stabilized zirconia implants].

OBJECTIVE: To evaluate the effects of surface treatment on the phase and fracture strength of yttria-and magnesia-stabilized and its mechanisms. METHODS: One-piece cylindrical screw-type implants were fabricated with yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) and magnesia partially stabilized zirconia (Mg-PSZ) using computer aided design (CAD)/computer aided manufacture (CAM) technique.They were divided into three groups: (1) placed in water for 1 h after final sintering (control group), (2) sandblasting using 110 µm Al2O3 particles, (3) sandblasting plus etching with hydrofluoric acid for 1 h.The surface morphology and roughness of the implants were evaluated.Tetragonal to monoclinic transformation was measured on the surface by X-ray diffraction.Static tests of the zirconia implants were carried out at room temperature following the International Standards Organization (ISO)14801:2014 Standard. RESULTS: Both sandblasting alone and sandblasting plus acid etching significantly increased surface roughness (Ra) of Mg-PSZ and Y-TZP implants (P < 0.01), with sandblasting plus acid etching exhibited the highest surface roughness.No monoclinic band was detected in Mg-PSZ surface.Compared with the control group, the surface monoclinic content of Mg-PSZ had no obvious change after surface treatments.However, strong monoclinic bands appeared in surface modified Y-TZP.Monoclinic content of Y-TZP was higher than that of control group (1.55%) after both sandblasting alone (16.44%) and sandblasting plus acid etching (7.68%).For Mg-PSZ implants, fracture strengths of sandblasting group and sandblasting plus acid etching group were (294.1±3.3) N and (331.3±26.4) N respectively, which were lower than that of control group (458.4±48.7) N with significant differences (P < 0.01).For Y-TZP implants, fracture strength of control group was (827.3±101.6) N.Compared with control group, sandblasting group showed significantly higher fracture strength (P=0.03), which was (1 162.9±116.5) N.While sandblasting plus acid etching group had a fracture strength of (867.2±171.0) N, with no significant difference with control group (P>0.99). CONCLUSION: Sandblasting improved the fracture strength of Y-TZP implants.For the Mg-PSZ implants manufactured in this study, surface treatments with sandblasting and sandblasting plus acid etching resulted in a decrease of fracture strength.

[Genetic mutation profiles for children with congenital hypothyroidism in Fujian province].

Objective: To explore the mutation characteristics of pathogenic genes in children with congenital hypothyroidism (CH) in Fujian. Methods: The clinical data of 116 unrelated CH children diagnosed in Fujian Provincial Maternal and Child Health Hospital from January 2019 to September 2020 were retrospectively analyzed, including 50 females and 66 males, with an average age of (20±10) days at diagnosis. Targeted exome sequencing technology was used to detect the mutation frequency, type and distribution characteristics of 29 genes related to thyroxine synthesis or thyroid development. Results: Three hundred and fifty-one potential functional mutations were detected in 105 of 116 CH patients, with a detection rate of 90.5% (105/116). DUOX2 (66.4%, 77/116) was the most frequent mutated gene, followed by TG (23.3%, 27/116), DUOXA1 (23.3%, 27/116), and TPO (12.1%, 14/116), which were all involved in thyroid hormone synthesis. Among the 105 children with CH, 70 cases carried double allele mutation. Except for 3 cases of thyroid dysplasia related genes (2 cases of TSHR and 1 case of GLIS3), the rest were also related to thyroid hormone synthesis. The gene with the highest carrier rate was DUOX2 (68.8%, 59/70), followed by TG (8.6%, 6/70), TPO (4.3%, 3/70), DUOXA2 (1.4%, 1/70) and DUOXA1 (1.4%, 1/70). Conclusion: The main mutated genes in CH children in Fujian are the key genes involved in thyroid hormone synthesis, such as DUOX2, TG and TPO.

[Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome].

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.

[Efficacy and feasibility of catheter-based adrenal ablation on Cushing's syndrome associated hypertension].

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.

Effects of reducing dietary cation-anion difference on lactation performance and nutrient digestibility of lactating cows and ammonia emissions from manure.

Reducing the dietary cation-anion difference (DCAD) reduces urine pH and, therefore, has potential to lower NH3 emissions from manure. We determined the effects of decreased DCAD on dry matter intake, production, nutrient digestibility, manure characteristics, and NH3 emissions from manure. An in vitro incubation study was conducted to evaluate the degree of reduced urine pH on manure pH and NH3 emissions from manure. In this study, urine pH was directly decreased from 8.5 to 7.5, 6.5, and 5.5 by adding sulfuric acid, which resulted in decreases in manure pH when manure was reconstituted with the fecal-to-urine ratio of 2:1 (as-is basis). The manures from urine at pH 7.5, 6.5, and 5.5 decreased NH3 emissions linearly by 19, 33, and 36%, respectively, compared with the manure from unacidified urine. An animal study was conducted with 27 mid-lactation Holstein cows in a randomized complete block design. Cows were blocked by parity and days in milk and assigned to 1 of 3 different DCAD diets: (1) HDCAD, a diet with DCAD of 193 mEq/kg of dry matter (DM); (2) MDCAD, a diet with 101 mEq/kg of DM; and (3) LDCAD, a diet with 1 mEq/kg of DM. A commercial anionic product (predominantly ammonium chloride) partly replaced urea, soybean meal, soyhulls, and corn grain in MDCAD and LDCAD to lower DCAD. The experiment lasted 7 wk (1-wk covariate followed by 6-wk data collection). Spot urine and fecal samples were collected for manure incubation. Data were analyzed using the MIXED procedure of SAS in a randomized block design. Dry matter intake and milk yield were not altered by treatments. No difference in milk fat content was observed among treatments, but fat yield tended to decrease linearly (1.00 to 0.86 kg/d) as DCAD decreased, resulting in a tendency for decreasing energy-corrected milk yield (35.1 to 32.7 kg/d). Milk protein content increased (3.00 to 3.14%) as DCAD decreased, but milk protein yield was not affected. Total-tract digestibility of DM, organic matter, and neutral detergent fiber did not differ among treatments. Digestibility of crude protein tended to decrease as DCAD decreased. There was no difference in fecal and urine N excretion among treatments, but fecal N as proportion of N intake tended to increase as DCAD decreased. Urine pH decreased linearly from 8.42 for HDCAD to 8.11 and 6.41 for MDCAD and LDCAD, respectively, resulting in decreased manure pH (7.57, 7.40, and 6.96 for HDCAD, MDCAD, and LDCAD, respectively). The cumulative NH3 emissions from manures over 6 d tended to decrease linearly as DCAD decreased (461 to 390 mg/kg of manure), but the decrease was only numerical when calculated on a cow basis (i.e., g/cow). In conclusion, lowering DCAD has potential to reduce NH3 emission from manure of lactating cows. However, a tendency for decreased milk fat yield and energy-corrected milk yield suggests that DCAD of 1 mEq/kg of DM may be too low, and more studies are needed to examine relatively less reduced DCAD to determine production responses in addition to NH3 emission from manure.

Development of ruminating behavior in Holstein calves between birth and 30 days of age.

Ruminating behavior accompanies the development of the rumen and the intake of solid feed in calves. However, few studies have reported on the emergence and development of rumination. In this study, we observed ruminating behavior changes of 56 Holstein calves (body weight at birth = 40.1 ± 3.96 kg; mean ± standard deviation) from birth to 30 d of age under the feeding management of suckling calves that were only fed pelleted concentrate feed and milk. All calves were housed in individual pens equipped with infrared cameras. We explored feed intake within 30 d of age, body weight on 61 d of age, and other apparent indicators, including the age of first eating the bedding, duration of non-nutritive oral behavior at 25 and 30 d of age, total starter feed intake within 30 d of age, average daily starter feed intake within 30 d of age, and duration of ruminating behavior at 25 and 30 d of age for all calves, to further explore the effects of the age of first ruminating behavior (AFR). The AFR fitted the normal distribution and ranged from 15 to 20 d of age for 50% of the experimental population. The AFR was positively correlated with the age of first eating the bedding and duration of non-nutritive oral behavior at 30 d of age. Total starter feed intake within 30 d of age, average daily starter feed intake within 30 d of age, duration of ruminating behavior at 25 and 30 d of age, and duration of eating the bedding at 25 and 30 d of age were negatively correlated with AFR. Overall, to the best of our knowledge, this is the first study that has analyzed the correlation between AFR and other indicators. We found that earlier AFR was associated with shorter duration of non-nutritive oral behavior, longer durations of rumination and eating the bedding, and higher feed intake by 30 d of age.

Vitrification by transient vacuum flashing spray cooling of liquid nitrogen.

BACKGROUND: The transient vacuum flashing spray cooling of liquid nitrogen (LN2) on a microstructured surface can provide ultra-fast cooling rate and may improve cell survival rates. OBJECTIVE: To utilize flashing spray cooling of LN2 instead of film boiling to improve further cell vitrification. METHOD: This study analyzed the effects of the three key parameters (flow rate of liquid nitrogen, ambient pressure, and spray distance) on the cooling process by experimentation. RESULTS: The experimental results showed that the vacuum flashing spray cooling of LN2 can gain higher cooling rates than that achieved by film boiling in conventional vitrification methods. The three parameters all affected the vacuum flash evaporation spray cooling of LN2, and their effect trends were not monotonous but followed a parabolic trend that increased and then decreased. That is, the three parameters all have optimum values to the cooling process. CONCLUSION: Vacuum flash evaporation spray cooling can develop the ultra-fast cooling rates needed to enhance cell vitrification. doi.org/10.54680/fr22310110212.

[The role and mechanism of tumor metastasis-associated gene 1 in radiosensitivity of HeLa cells].

Objective: To determine the effect of tumor metastasis-associated gene 1 (MTA1) on the sensitivity of HeLa cells to radiotherapy, and to clarify its molecular mechanism. Methods: The transcriptome differences between MTA1 knocked down Hela cells and control cells were analyzed, and the differentially expressed genes (DEGs) was used to perform Gene-Set Enrichment Analysis (GSEA) and Gene Ontology (GO) cluster analysis. Flow cytometry was used to detect apoptosis in MTA1-overexpressed HeLa cells and control cells before and after 10 Gy X-ray irradiation. Cloning formation assay and real-time cellular analysis (RTCA) were used to monitor the cell proliferation before and after 2 Gy X-ray irradiation. To dissect the underlying molecular mechanisms of MTA1 affecting the sensitivity of radiotherapy, the proteins encoded by the DEGs were selected to construct a protein-protein interaction network, the expression of γ-H2AX was detected by immunofluorescence assay, and the expression levels of γ-H2AX, ß-CHK2, PARP and cleaved caspase 3 were measured by western blot. Results: By transcriptome sequencing analysis, we obtained 649 DEGs, of which 402 genes were up-regulated in MTA1 knockdown HeLa cells and 247 genes were down-regulated. GSEA results showed that DEGs associated with MTA1 were significantly enriched in cellular responses to DNA damage repair processes. The results of flow cytometry showed that the apoptosis rate of MTA1 over-expression group (15.67±0.81)% after 10 Gy X-ray irradiation was significantly lower than that of the control group [(40.27±2.73)%, P<0.001]. After 2 Gy X-ray irradiation, the proliferation capacity of HeLa cells overexpressing MTA1 was higher than that of control cells (P=0.024). The numbers of colon in MTA1 over-expression group before and after 2 Gy X-ray irradiation were (176±7) and (137±7) respectively, higher than (134±4) and (75±4) in control HeLa cells (P<0.05). The results of immunofluorescence assay showed that there was no significant expression of γ-H2AX in MTA1 overexpressed and control HeLa cells without X-ray irradiation. Western blot results showed that the expression level of ß-CHK2 in MTA1-overexpressing HeLa cells (1.04±0.06) was higher than that in control HeLa cells (0.58±0.25, P=0.036) after 10 Gy X-ray irradiation. The expression levels of γ-H2AX, PARP, and cleaved caspase 3 were 0.52±0.13, 0.52±0.22, and 0.63±0.18, respectively, in HeLa cells overexpressing MTA1, which were lower than 0.87±0.06, 0.78±0.12 and 0.90±0.12 in control cells (P>0.05). Conclusions: This study showed that MTA1 is significantly associated with radiosensitivity in cervical cancer HeLa cells. MTA1 over-expression obviously reduces the sensitivity of cervical cancer cells to X-ray irradiation. Mechanism studies initially indicate that MTA1 reduces the radiosensitivity of cervical cancer cells by inhibiting cleaved caspase 3 to suppress apoptosis and increasing ß-CHK2 to promote DNA repair.

[Clinical research progress and implications of therapeutic vaccines for cervical cancer and precancerous lesions: a qualitative systematic review].

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.

[Efficacy of combined application of glycine powder air-polishing in non-surgical treatment of peri-implant diseases].

OBJECTIVE: To compare the clinical efficacy of combined application of glycine powder air-polishing and mechanical submucosal debridement in non-surgical treatment of peri-implant diseases. METHODS: A randomized controlled clinical study was carried out on patients diagnosed with peri-implant diseases in the Department of Periodontology, Peking University School and Hospital of Stomatology, between May of 2020 and June of 2021.Twenty-eight patients with totally sixty-two implants were enrolled.The patients were randomly divided into the test group and control group. The patients in the test group (13 subjects/32 implants) received mechanical submucosal debridement using titanium curettes combined with application of glycine powder air-polishing, while the control group (15 subjects/30 implants) received mechanical submucosal debridement using titanium only. Clinical parameters, such as plaque index (PLI), pocket probing depth (PPD), bleeding index (BI) and the percentage of suppuration on probing on implants' level (SoP%) were measured at baseline and 8 weeks after non-surgical intervention. Changes and group differences of clinical parameters of the implants before and 8 weeks after non-surgical intervention were compared. RESULTS: Mean PLI, PPD, BI of both the test group and control group significantly reduced 8 weeks after non-surgical intervention (P < 0.05). Compared with the control group, the test group achieved lower BI (2.7±0.8 vs. 2.2±0.7, P < 0.05), more reduction of BI (0.6±0.7 vs. 1.1±0.6, P < 0.01) and more reduction of SoP% (21.9% vs. 10%, P < 0.05) after non-surgical intervention. Both the control and test groups exhibited comparable PLI and PPD reductions (P>0.05). For the implants diagnosed with peri-implant mucositis, the test group revealed more signi-ficant reduction in BI and SoP% than the control group (1.0±0.7 vs. 0.4±0.7, P=0.02; 6.3% vs. 0, P=0.012). There was no significant difference existing in PLI and PD improvement between the control group and test group (P>0.05). For the implants diagnosed with peri-implantitis, there was no significant difference existing in PLI, PPD, BI and SoP% improvement values between the test and control groups (P>0.05). No complications or discomforts were reported during the study. CONCLUSION: Both treatment procedures could relieve the inflammation of peri-implant soft tissue. Non-surgical mechanical submucosal debridement combined application of glycine powder air-polishing is associated with significant reduction of soft tissue bleeding and suppuration on probing especially in the implants diagnosed with peri-implant mucositis.

[Validation of prognostic value of pathological staging in pathological stage â lung adenocarcinoma].

Objectives: To examine the prognostic significance of WHO classification of lung adenocarcinoma in 2021 in patients with stage Ⅰ pulmonary adenocarcinoma. Methods: The clinical data of 829 patients who underwent surgery from January 2015 to September 2016 at Department of Thoracic Surgery, Zhongshan Hospital of Fudan University and had a postoperative pathologically confirmed diagnosis of stage Ⅰ lung adenocarcinoma were analyzed retrospectively. There were 389 males and 440 females, aged (60±11) years (range: 32 to 90 years), including 570 cases with solid nodules, 259 cases with ground-glass nodule. The survival curve was plotted using the Kaplan-Meier method and compared by the Log-rank test. The Cox proportional hazards regression model was used to identify prognosis factors on overall survival (OS), and recurrence-free survival (RFS). Results: Among the 829 patients, 470 cases were acinar predominant type, 165 cases were papillary predominant type, 90 cases were lepidic predominant type, 62 cases were solid predominant type, and 42 cases were micropapillary type. Compared with the solid nodule group, the proportion of patients with lepidic predominant type was higher in the ground glass nodule group (20.5%(53/259) vs. 6.5%(37/570), χ²=35.922, P<0.01), while the proportion of micropapillary (1.2%(3/259) vs. 6.8%(39/570), χ²=11.961, P<0.01) and solid predominant type (1.5%(4/259) vs. 10.2%(58/570), χ²=19.172, P<0.01) was lower. Survival analysis of 829 patients showed that patients with the lepidic predominant had the best prognosis, those with acinar and papillary predominant were worse, and patients with solid and micropapillary predominant had the worst prognosis (all P<0.01). The independent prognosis factors associated with postoperative recurrence were T2 stage (HR=1.631, 95%CI: 1.030 to 2.583, P=0.037), pathologic subtype (P=0.036), presence of a micropapillary component (HR=1.764, 95%CI: 1.143 to 2.722, P=0.010), and solid nodule in CT picture (HR=18.690, 95%CI: 7.587 to 46.043, P<0.01). Subgroup analysis showed that in both solid and ground-glass nodules, the presence of a solid-type component was a prognosis factor for overall survival, and the presence of a micropapillary component was a prognosis factor for recurrence-free survival. Conclusions: The presence of micropapillary and solid component, in addition to histological subtype, are prognosis factors for patients with stage Ⅰ lung adenocarcinoma. For patients with stage Ⅰ lung adenocarcinoma, the combination of pathological subtype and T-stage is more valuable and reliable for prognosis.