ABSTRACT Introduction: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). Materials and Methods: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. Results: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). Conclusions: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required. Introduction KDSurgical KD Surgical Robot01 Robot 01 Robot-0 KDSR01 KDSR SR (KD-SR-01 (DV robotassisted robot assisted RARNU. . (RARNU) Methods 202 2023 KDRARNU. KDRARNU KD-RARNU DVRARNU. DVRARNU DV-RARNU data followup follow up Results 100 margins 242 [24 120951 120 951 (120-951 25 62498 62 498 (62-498 0.780, 0780 0.780 , 0 780 0.780] 137 [13 55290 55 290 (55-290 10 62220 220 (62-220 0.114, 0114 0.114 114 0.114] 207 [20 121460 121 460 (121-460 18 96305 96 305 (96-305 0.091, 0091 0.091 091 0.091] [5 10600 600 (10-600 5 10700 700 (10-700 0.507, 0507 0.507 507 0.507] scores metastasis recurrence equipmentrelated equipment related fourweek four week followup. up. 3.4% 34 3 4 (3.4% ClavienDindo Clavien Dindo III. III III) Conclusions KD-SR-0 required Robot0 Robot- KDSR0 (KD-SR-0 (RARNU 20 24 [2 12095 12 95 (120-95 6249 6 49 (62-49 078 0.78 78 13 [1 5529 (55-29 6222 22 (62-22 011 0.11 11 12146 46 (121-46 9630 9 30 (96-30 009 0.09 09 [ 1060 60 (10-60 1070 70 (10-70 050 0.50 3.4 (3.4 KD-SR- (KD-SR- 1209 (120-9 624 (62-4 07 0.7 7 552 (55-2 622 (62-2 0.1 1214 (121-4 963 (96-3 00 0.0 106 (10-6 107 (10-7 05 0.5 3. (3. KD-SR (KD-SR (120- (62- 0. (55- (121- (96- (10- (3 (120 (62 (55 (121 (96 (10 ( (12 (6 (5 (9 (1

ABSTRACT Objectives: To evaluate the safety and effectiveness of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC), and open radical cystectomy (ORC) in bladder cancer. Methods: A literature search for network meta-analysis was conducted using international databases up to February 29, 2024. Outcomes of interest included baseline characteristics, perioperative outcomes and oncological outcomes. Results: Forty articles were finally selected for inclusion in the network meta-analysis. Both LRC and RARC were associated with longer operative time, smaller amount of estimated blood loss, lower transfusion rate, shorter time to regular diet, fewer incidences of complications, and fewer positive surgical margin compared to ORC. LRC had a shorter time to flatus than ORC, while no difference between RARC and ORC was observed. Considering lymph node yield, there were no differences among LRC, RARC and ORC. In addition, there were statistically significant lower transfusion rates (OR=-0.15, 95% CI=-0.47 to 0.17), fewer overall complication rates (OR=-0.39, 95% CI=-0.79 to 0.00), fewer minor complication rates (OR=-0.23, 95% CI=-0.48 to 0.02), fewer major complication rates (OR=-0.23, 95% CI=-0.68 to 0.21), fewer positive surgical margin rates (OR=0.22, 95% CI=-0.27 to 0.68) in RARC group compared with LRC group. Conclusion: LRC and RARC could be considered as a feasible and safe alternative to ORC for bladder cancer. Notably, compared with LRC, RARC may benefit from significantly lower transfusion rates, fewer complications and lower positive surgical margin rates. These data thus showed that RARC might improve the management of patients with muscle invasive or high-risk non-muscle invasive bladder cancer. Objectives robotassisted robot assisted RARC, , (RARC) (LRC) (ORC cancer Methods metaanalysis meta analysis 29 2024 characteristics Results metaanalysis. analysis. loss rate diet observed yield addition OR=0.15, OR015 OR OR= 0.15, 0 15 (OR=-0.15 95 CI=0.47 CI047 CI CI= 0.47 47 CI=-0.4 0.17, 017 0.17 17 0.17) OR=0.39, OR039 0.39, 39 (OR=-0.39 CI=0.79 CI079 0.79 79 CI=-0.7 0.00, 000 0.00 00 0.00) OR=0.23, OR023 0.23, 23 (OR=-0.23 CI=0.48 CI048 0.48 48 0.02, 002 0.02 02 0.02) CI=0.68 CI068 0.68 68 CI=-0.6 0.21, 021 0.21 21 0.21) OR=0.22, OR022 22 (OR=0.22 CI=0.27 CI027 0.27 27 CI=-0.2 068 Conclusion Notably highrisk high risk nonmuscle non (RARC (LRC 2 202 OR=0.15 OR01 015 0.15 1 (OR=-0.1 9 CI=0.4 CI04 047 0.4 4 CI=-0. 01 0.1 OR=0.39 OR03 039 0.39 3 (OR=-0.3 CI=0.7 CI07 079 0.7 7 0.0 OR=0.23 OR02 023 0.23 (OR=-0.2 048 CI=0.6 CI06 0.6 6 0.2 OR=0.22 (OR=0.2 CI=0.2 CI02 027 06 20 OR=0.1 OR0 (OR=-0. CI=0. CI0 04 0. CI=-0 OR=0.3 03 0.3 07 OR=0.2 (OR=0. OR=0. (OR=-0 CI=0 CI=- (OR=0 OR=0 (OR=- (OR= (OR

ABSTRACT Objective: To evaluate objective treatment efficacy and safety, and subjective patient-reported outcomes in patients with complex ureteral strictures (US) undergoing minimally invasive lingual mucosal graft ureteroplasty (LMGU). Materials and Methods: We prospectively enrolled patients underwent robotic or laparoscopic LMGU between May 2020 and July 2022. Clinical success was defined as symptom-free and no radiographic evidence of re-obstruction. Patient-reported outcomes, including health-related quality of life (HRQoL), mental health status and oral health-related quality of life (OHRQoL), were longitudinally evaluated before surgery, 6 and 12 months postoperatively. Results: Overall, 41 consecutive patients were included. All procedures were performed successfully with 32 patients in robotic approach and 9 in laparoscopic. Forty (97.56%) patients achieved clinical success during the median follow-up of 29 (range 15-41) months. Although patients with complex US experienced poor baseline HRQoL, there was a remarkable improvement following LMGU. Specifically, the 6-month and 12-month postoperative scores were significantly improved compared to the baseline (p < 0.05) in most domains. Twenty-eight (68.3%) and 31 (75.6%) patients had anxiety and depression symptoms before surgery, respectively. However, no significant decrease in the incidence of these symptoms was observed postoperatively. Moreover, there was no significant deterioration of OHRQoL at 6 months and 12 months postoperatively when compared to the baseline. Conclusions: LMGU is a safe and efficient procedure for complex ureteral reconstruction that significantly improves patient-reported HRQoL without compromising OHRQoL. Assessing patients’ quality of life enables us to monitor postoperative recovery and progress, which should be considered as one of the criteria for surgical success. Objective safety patientreported patient reported (US . (LMGU) Methods 202 2022 symptomfree symptom free reobstruction. reobstruction re obstruction. obstruction re-obstruction Patientreported Patient healthrelated related , (HRQoL) OHRQoL, (OHRQoL) surgery 1 Results Overall 4 included 3 97.56% 9756 97 56 (97.56% followup follow up 2 range 1541 15 15-41 Specifically 6month month 12month p 0.05 005 0 05 domains Twentyeight Twenty eight 68.3% 683 68 (68.3% 75.6% 756 75 (75.6% respectively However Moreover Conclusions progress (LMGU 20 (HRQoL (OHRQoL 97.56 975 5 (97.56 154 15-4 0.0 00 68.3 (68.3 75.6 7 (75.6 97.5 (97.5 15- 0. 68. (68. 75. (75. 97. (97. (68 (75 (97 (6 (7 (9 (

Abstract Slender reed straws in nature can withstand heavy weight of reed spikes and lateral wind force, and thus show good mechanical properties, especially compression resistance and shear resistance. In the paper, the quasi-static and dynamic mechanical properties of reed straws were studied. Three influencing factors of the straws were set according to the nodes (node-containing, node-free), location section (location 1, 2, 3, 4, 5), and moisture content (low, medium, high). The tensile strength of node-free reed straws with low moisture content ranged from 55.40 to 68.14 MPa at different locations. The axial compressive strength of node-containing straws was higher than that of node-free straws, and the influence of moisture content on the axial compressive strength was more obvious. The radial compressive strength of node-containing straws is 13.00 times higher than that of node-free straws in the corresponding part. The bending strength of straws gradually increases from the top to the root, and it is further enhanced with higher moisture content. The axial impact peak load of node-containing straws is up to 1.27 times that of node-free straws, and the axial impact peak load of straws with high moisture content is 1.40 times higher than that of straws with low moisture content in the corresponding part. The radial impact strength of reed straws gradually increases from the top to the root. In terms of bending impact strength, the impact toughness of reed straws ranges from 0.030 to 0.14 J·cm2, and the specific energy absorption ranges from 1.09 to 4.35 J/kg. Because of the excellent mechanical properties, reed straws provide important material performance data for the engineering field and inspire the design of new engineering materials or structures by improving strength and reducing weight. force paper quasistatic quasi static studied nodecontaining, nodecontaining node containing, containing (node-containing nodefree, nodefree free , node-free) 1 2 3 4 5, 5 5) low, (low medium high. . high) 5540 55 40 55.4 6814 68 14 68.1 locations obvious 1300 13 00 13.0 part root 127 27 1.2 140 1.4 0030 0 030 0.03 014 0.1 Jcm2 Jcm J cm2 cm J·cm2 109 09 1.0 435 35 4.3 Jkg kg J/kg 554 55. 681 6 68. 130 13. 12 1. 003 03 0.0 01 0. J·cm 10 43 4.

ABSTRACT The study aimed to investigate the effect of methionine deficiency on conventional nutrient composition, NO and NOS activity in the liver and kidney, and expression of genes related to the NF-κB signal pathway. One hundred 1-day-old broilers were divided into control and methionine deficiency group, and provided with a standard diet. The methionine-deficient group was fed with a methionine-deficient diet for 42 days. Moisture content, protein content, and crude lipid content were determined by freeze drying, the Kjeldahl method, and the ether extraction method. The concentration of NO was measured using the nitrate reductase method, and the activity of NOS was measured using colorimetry. mRNA expression of related genes in the NF-κB signal pathway was detected by reverse transcription-polymerase chain reaction (RT-PCR). The results showed the contents of crude protein and crude lipid in the liver and kidney of the methionine-deficient group were significantly higher than those in the control group (p<0.05 or p<0.01). There was no significant change in dry matter (p>0.05). Methionine deficiency resulted in significantly increased NO concentration and total nitric oxide synthase (TNOS) activities in the liver and kidney (p<0.01). In contrast, cNOS and inducible iNOS activities significantly decreased (p<0.01). The expression of NF-κB, TNF-α, IFN-γ, IL-1, and IL-6 mRNA, which are related to the NF-κB signal pathway of the methionine-deficient group, were significantly higher than those in the control group (p<0.05 or p<0.01). It is concluded that long-term feeding diets lacking methionine will lead to changes in nutrient composition and inflammatory injury of the liver and kidney. NFκB NF κB 1dayold dayold 1 day old methioninedeficient deficient 4 days drying method colorimetry transcriptionpolymerase transcription polymerase RTPCR. RTPCR RT PCR . (RT-PCR) p<0.05 p005 p 0 05 (p<0.0 p<0.01. p001 p<0.01 01 p<0.01) p>0.05. p>0.05 (p>0.05) TNOS (TNOS (p<0.01) contrast NFκB, κB, TNFα, TNFα TNF α, α TNF-α IFNγ, IFNγ IFN γ, γ IFN-γ IL1, IL1 IL 1, IL-1 IL6 6 IL- longterm long term (RT-PCR p<0.0 p00 (p<0. p>0.0 (p>0.05 (p<0.01 p<0. p0 (p<0 p>0. (p>0.0 p<0 (p< p>0 (p>0. p< (p p> (p>0 (p>

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway. (UC inflammation diverse Angiopoietinlike Angiopoietin like ANGPT (ANGPT2 diseases However far patients DSSinduced DSS induced suppressed detected stress immunohistochemistry immunofluorescence kits Finally NLRP inflammasomerelated proteins autophagymediated autophagy mediated (ANGPT

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy. vaccines TSAmodified modified vivo TSAtreated treated Nutu19 Nutu 19 Nutu-1 Xray X ray staining GMCSF, GMCSF GM CSF, CSF GM-CSF IL7, IL7 IL 7, 7 IL-7 IL17, IL17 17, 17 IL-17 LIF LIX KC MCP1, MCP1 MCP 1, 1 MCP-1 MIP2, MIP2 MIP 2, 2 MIP-2 MCSF, MCSF M M-CSF IP10/CXCL10, IP10CXCL10 IPCXCL IP 10/CXCL10, 10 CXCL10 CXCL IP-10/CXCL10 MIGCXCL9 MIGCXCL MIG CXCL9 MIG/CXCL9 RANTES IL4, IL4 4, 4 IFNγ, IFNγ IFN γ, γ immunoassay cellmediated mediated tumorbearing bearing CD4 CD CD8 P<0.05. P005 P P<0.05 . 0 05 (P<0.05) extent IL- effect exposure progression system rates Nutu1 Nutu- IL1 IL-1 MCP- MIP- IP10 IP10/CXCL10 IP10CXCL1 10CXCL10 10/CXCL10 CXCL1 IP-10/CXCL1 MIG/CXCL P00 P<0.0 (P<0.05 IP1 IP10/CXCL1 IP10CXCL 10CXCL1 10/CXCL1 IP-10/CXCL P0 P<0. (P<0.0 IP10/CXCL 10CXCL 10/CXCL P<0 (P<0. P< (P<0 (P< (P

Abstract The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis. worldwide (MR (SNP varianceweighted variance (IVW fixedeffect fixed randomeffect random OR=1.032 OR1032 OR 1 032 (OR=1.032 95%CI 95CI CI 95 0.9231.153 09231153 0.923 1.153 0 923 153 0.923-1.153 P=0.574 P0574 P 574 0.9201.158 09201158 0.920 1.158 920 158 0.920-1.158 P0588 588 P=0.588 respectively. respectively . respectively) OR=1.031 OR1031 031 (OR=1.031 0.7801.361, 07801361 0.780 1.361, 780 361 0.780-1.361 P=0.835, P0835 P=0.835 , 835 P=0.835) OR=1.120 OR1120 120 (OR=1.120 0.9441.328, 09441328 0.944 1.328, 944 328 0.944-1.328 P=0.229, P0229 P=0.229 229 P=0.229) OR=1.003 OR1003 003 (OR=1.003 0.8391.197, 08391197 0.839 1.197, 839 197 0.839-1.197 P=0.977, P0977 P=0.977 977 P=0.977) OR=1.078 OR1078 078 (OR=1.078 0.9211.262, 09211262 0.921 1.262, 921 262 0.921-1.262 P=0.346, P0346 P=0.346 346 P=0.346) 1.078 1078 0.9191.264, 09191264 0.919 1.264, 919 264 0.919-1.264 P=0.351, P0351 P=0.351 351 P=0.351) MREgger Egger OR=1.360 OR1360 360 (OR=1.360 0.9981.853, 09981853 0.998 1.853, 998 853 0.998-1.853 P=0.092. P0092 P=0.092 092 P=0.092) Q=7.454, Q7454 Q 7 454 (Q=7.454 P0489 489 P=0.48 Q3901 3 901 Q=3.901 P0791 791 P=0.791 intercept (intercept 0.004 0004 004 -0.004 P=0.101. P0101 P=0.101 101 P=0.101) leaveoneout leave one out OR=1.03 OR103 03 (OR=1.03 9231 0.9231.15 0923115 0923 0.92 1153 1.15 92 15 0.923-1.15 P=0.57 P057 57 9201 0.9201.15 0920115 0920 1158 0.920-1.15 P058 58 P=0.58 7801 0.7801.361 0780136 0780 0.78 1361 1.361 78 36 0.780-1.36 P083 P=0.83 83 OR=1.12 OR112 12 (OR=1.12 9441 0.9441.328 0944132 0944 0.94 1328 1.328 94 32 0.944-1.32 P022 P=0.22 22 OR=1.00 OR100 00 (OR=1.00 8391 0.8391.197 0839119 0839 0.83 1197 1.197 19 0.839-1.19 P097 P=0.97 97 OR=1.07 OR107 07 (OR=1.07 9211 0.9211.262 0921126 0921 1262 1.262 26 0.921-1.26 P034 P=0.34 34 1.07 107 9191 0.9191.264 0919126 0919 0.91 1264 1.264 91 0.919-1.26 P035 P=0.35 35 OR=1.36 OR136 (OR=1.36 9981 0.9981.853 0998185 0998 0.99 1853 1.853 99 85 0.998-1.85 P009 P=0.09 09 Q=7.454 Q745 45 (Q=7.45 P048 48 P=0.4 Q390 90 Q=3.90 P079 79 P=0.79 0.00 000 -0.00 P010 P=0.10 10 OR=1.0 OR10 (OR=1.0 0.9231.1 092311 0.9 115 1.1 0.923-1.1 P=0.5 P05 5 0.9201.1 092011 0.920-1.1 0.7801.36 078013 0.7 136 1.36 0.780-1.3 P08 P=0.8 8 OR=1.1 OR11 (OR=1.1 0.9441.32 094413 094 132 1.32 0.944-1.3 P02 P=0.2 2 0.8391.19 083911 083 0.8 119 1.19 0.839-1.1 P09 P=0.9 0.9211.26 092112 126 1.26 0.921-1.2 P03 P=0.3 1.0 0.9191.26 091912 091 0.919-1.2 OR=1.3 OR13 (OR=1.3 0.9981.85 099818 099 185 1.85 0.998-1.8 P00 P=0.0 Q=7.45 Q74 4 (Q=7.4 P04 P=0. Q39 Q=3.9 P07 P=0.7 0.0 -0.0 P01 P=0.1 OR=1. OR1 (OR=1. 0.9231. 09231 0. 11 1. 0.923-1. P0 0.9201. 09201 0.920-1. 0.7801.3 07801 13 1.3 0.780-1. 0.9441.3 09441 0.944-1. 0.8391.1 08391 08 0.839-1. 0.9211.2 09211 1.2 0.921-1. 0.9191.2 09191 0.919-1. 0.9981.8 09981 18 1.8 0.998-1. Q=7.4 Q7 (Q=7. P=0 Q3 Q=3. -0. OR=1 (OR=1 0.9231 0.923-1 0.9201 0.920-1 0.7801. 0.780-1 0.9441. 0.944-1 0.8391. 0.839-1 0.9211. 0.921-1 0.9191. 0.919-1 0.9981. 0.998-1 Q=7. (Q=7 P= Q=3 -0 OR= (OR= 0.923- 0.920- 0.7801 0.780- 0.9441 0.944- 0.8391 0.839- 0.9211 0.921- 0.9191 0.919- 0.9981 0.998- Q=7 (Q= Q= - (Q

Abstract We aimed to develop a prognostic model for primary pontine hemorrhage (PPH) patients and validate the predictive value of the model for a good prognosis at 90 days. A total of 254 PPH patients were included for screening of the independent predictors of prognosis, and data were analyzed by univariate and multivariable logistic regression tests. The cases were then divided into training cohort (n=219) and validation cohort (n=35) based on the two centers. A nomogram was developed using independent predictors from the training cohort to predict the 90-day good outcome and was validated from the validation cohort. Glasgow Coma Scale score, normalized pixels (used to describe bleeding volume), and mechanical ventilation were significant predictors of a good outcome of PPH at 90 days in the training cohort (all P<0.05). The U test showed no statistical difference (P=0.892) between the training cohort and the validation cohort, suggesting the model fitted well. The new model showed good discrimination (area under the curve=0.833). The decision curve analysis of the nomogram of the training cohort indicated a great net benefit. The PPH nomogram comprising the Glasgow Coma Scale score, normalized pixels, and mechanical ventilation may facilitate predicting a 90-day good outcome. (PPH 9 25 tests n=219 n219 n 219 (n=219 n=35 n35 35 (n=35 centers 90day day score used volume, volume , volume) all P<0.05. P005 P P<0.05 . 0 05 P<0.05) P=0.892 P0892 892 (P=0.892 well area curve=0.833. curve0833 curve=0.833 833 curve=0.833) benefit 2 n=21 n21 21 (n=21 n=3 n3 3 (n=3 P00 P<0.0 P=0.89 P089 89 (P=0.89 curve083 curve=0.83 83 n=2 n2 (n=2 n= (n= P0 P<0. P=0.8 P08 8 (P=0.8 curve08 curve=0.8 (n P<0 P=0. (P=0. curve0 curve=0. P< P=0 (P=0 curve=0 P= (P= curve= (P

Abstract The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis. remodeling Osteoporosis ageassociated disease architecture Nevertheless (ECs enigmatic study DEGs (DEGs GEO (GEO GSE148804 GSE (GSE148804 tools approach Adamts1 Adamts Adamts2 Adamts4 Adamts14 Col5a1 Cola Col Col5a2 Subsequently miRNAmRNA miRNA mRNA CDhiEMCNhi CD hiEMCNhi CDlowEMCNlow lowEMCNlow prediction miR466i3p miRip miR 466i 3p i p miR466i5p 5p agerelated related osteoporosis GSE14880 (GSE14880 Col5a GSE1488 (GSE1488 GSE148 (GSE148 GSE14 (GSE14 GSE1 (GSE1 (GSE

Abstract Background Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. Methods S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). Results The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). Conclusions Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae. S (S prevention period 201 2014 antisera 1 Etest E test method (STs MLST. MLST . (MLST) F 32.9 329 32 9 (32. , %) A 20.7 207 20 7 (20. 10.7 107 10 (10. 10.0 0 8.6 86 8 6 (8. 13.6 136 (13. 12.9 129 12 (12. B 7.9 79 (7. %. 13valent valent PCV (PCV groups penicillin cefuroxime imipenem erythromycin trimethoprimsulfamethoxazole trimethoprim sulfamethoxazole 71 7. 928 92 92. 657 65 65. 850 85 85. respectively 07 0. 500 50 50. 386 38 38. 964 96 4 96. CC CC27 43.6 436 43 (43. 143 3 14. vaccinerelated vaccine related Therefore PCV1 (MLST 32. (32 20. 2 (20 10. (10 8. (8 13. (13 12. (12 (7 5 CC2 43. (43 (3 (2 (1 ( (4

Previous studies show that glycogen synthase kinase 3β (GSK3B) plays an important role in tumorigenesis. However, its role in cervical cancer is unclear. The present study silenced GSK3B with siRNAs and/or chemical inhibitors to determine its role in HeLa cervical cancer cell proliferation and migration as well as in xenograft tumor growth. Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine cell survival and proliferation. Scratch and Transwell® assays were used to evaluate cell migration. Xenograft tumors were used to evaluate the effect of GSK3B on tumor growth. Transcriptomic sequencing was used to clarify the mechanisms underlying the foregoing processes. Public databases and clinical specimens showed that GSK3B was upregulated in cervical cancer tissues and correlated with poor prognosis. In vitro experiments indicated that GSK3B inhibition reduced cell viability, proliferation, and migration. In vivo experiments demonstrated that GSK3B inhibition slowed xenograft tumor growth. Transcriptomic sequencing revealed that GSK3B inhibition modulated the phosphatidylinositol 3-carboxykinase (PI3K)/protein kinase B (Akt) and extracellular matrix (ECM)-receptor interaction signaling pathways. GSK3B inhibition decreased the protein levels of phosphorylated PI3K and Akt and the levels of mesenchymal markers but increased those of epithelial markers. An activator of the PI3K/Akt signaling pathway counteracted the suppressive effects of GSK3B inhibition on HeLa cell viability and proliferation and on PI3K/Akt signaling. Our data suggested that GSK3B regulated cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition (EMT). β GSKB GSK (GSK3B tumorigenesis However unclear andor or growth CCK8 CCK 8 (CCK)- 5ethynyl2deoxyuridine ethynyldeoxyuridine 5 ethynyl 2 deoxyuridine EdU (EdU Transwell processes prognosis 3carboxykinase carboxykinase 3 PI3K/protein PI3Kprotein PIKprotein /protein PI K (Akt ECMreceptor ECM receptor pathways PIK PI3KAkt PIKAkt epithelialtomesenchymal EMT. EMT . (EMT) (CCK) Kprotein KAkt (EMT (CCK

Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells. Q Q1 CoQ (CoQ10 determined process RAW2647 RAW RAW264 7 RAW264. NFκB NF κB RANKL (RANKL assessed CoQ1 andor HO H O H2O (ROS PI3KAKTmTOR PIKAKTmTOR PI3K AKT mTOR PI K tested Moreover agonist autophagyrelated related measured TRAPpositive TRAP positive PIK ERK p p3 reduced FOXO3LC3Beclin1 FOXOLCBeclin FOXO3 LC3 Beclin1 FOXO LC Beclin FOXO3/LC3/Beclin augmented results RANKLinduced induced (CoQ1 RAW26 KAKTmTOR FOXO3LC3Beclin (CoQ RAW2

Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine. kidney liver transplants (AEs FAERS. . (FAERS) ROR, ROR , (ROR) PRR, PRR (PRR) BCPNN, BCPNN (BCPNN) EBGM. EBGM (EBGM) 19582 19 582 19,58 201 2022 cases 3911 3 911 3,91 47 Cyclosporininduced Cyclosporin induced 2 SOCs. SOCs (SOCs) Notably disorders injury poisoning complications label Furthermore others Moreover ADRs, (ADRs) decrease Importantly (FAERS (ROR (PRR (BCPNN (EBGM 1958 1 58 19,5 20 202 391 91 3,9 4 (SOCs (ADRs 195 5 19, 39 9 3,

The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity. 5fluorouracil fluorouracil 5 5Fu, 5Fu Fu , (5-Fu) agent welldocumented documented effects Nevertheless RES, (RES) antitumor anti properties agents investigation models cytotoxicity coadministration co administration viability migration invasion volume Mechanistically p53mediated pmediated mediated p autophagy effect Notably cardiomyocytes p5 expression Bcl2 Bcl 2 Bcl- levels 5Fuinduced Fuinduced cardiotoxicity summary Fu, (5-Fu (RES