Objective To analyze the rotavirus(RV) vaccine coverage among children in the birth cohorts in Shijingshan District of Beijing from 2015 to 2023, so as to provide a scientific support for RV vaccination.Methods The data were collected through the Beijing Immunization Planning Information Management System, and descriptive epidemiological methods were used for statistical analysis.Results A total of 36 248 doses of RV vaccines were inoculated among children born in Shijingshan District of Beijing from 2015 to 2023, and the overall coverage levels for the first, second, and third doses were 43. 03%, 28. 55% and 18. 72%, respectively. The vaccination rate had shown an overall upward trend over the years(χ~2_(trend)= 4 554. 383, 8 016. 090 and 9 143. 411, respectively, each P < 0. 001). The coverage levels for the first, second, and third doses of Lanzhou lamprotavirus vaccine(LLR) were 22. 91%, 9. 04% and 1. 28% among the 2015-2023 birth cohorts respectively, and the vaccination rate had shown an upward trend followed by a downward trend with the years. The coverage levels for the first, second, and third doses of pentavalent human-bovine reassortant rotavirus vaccine(RV5) among the 2018-2023 birth cohorts were 33. 30%, 32. 30% and 28. 87%, respectively, and the vaccination rate had shown an overall upward trend over the years(χ~2_(trend)= 3 745. 642, 3 402. 195 and 3 237. 052, respectively, each P < 0. 001). The vaccination rates of the first, second, and third doses of LLR and RV5 in different regions showed statistically significant differences(LLR: χ~2=1 244. 175, 1 100. 036 and 44. 453, respectively, each P < 0. 001; RV5: χ~2= 649. 139, 567. 390 and 464. 887, respectively,each P < 0. 001), with a gradual increasing trend from west to east area.Conclusion The vaccination rate of RV vaccine among children born in Shijingshan District of Beijing from 2015 to 2023 is relatively low, and it is necessary to further strengthen publicity and enhance parental awareness, so as to increase the RV vaccination rate for the effective prevention of childhood RV diarrhea.

Objective To design and fabricate an integrated optoelectrical fiber to enable the simultaneous transmission of high-power laser and electrical current, thereby developing a novel tool for urological surgery.Methods A miniature metal sleeve was installed at the front end of a medical high-energy optical fiber, and corresponding conductive circuits were configured. The fiber was connected to a fiber thulium laser and a bipolar plasma generator simultaneously. Experiments of simulated vaporization were conducted on ex vivo porcine kidney tissues using thulium laser (50 W), plasma (100 W), and thulium laser + plasma (50 W+100 W), respectively. Tissue removal efficiency was calculated using the weighing method:tissue clearance rate (g/min)=[mass before vaporization (g) - mass after vaporization (g)]/vaporization time (min). Lateral tissue thermal damage was assessed with hematoxylin-eosin (HE) staining. One-way analysis of variance and least significant difference test were used for statistical analysis.Results The integrated optoelectrical fiber was successfully constructed, which could simultaneously and continuously transmit thulium laser and plasma electrocision current. The tissue clearance rate of the thulium laser+plasma group was significantly higher than that of the thulium laser group and plasma group [(0.49±0.13) g/min vs. (0.14±0.02) g/min vs. (0.11±0.04) g/min, P＜0.001]. The average lateral thermal damage depth of the thulium laser + plasma group showed no statistically significant difference compared to the thulium laser group [(985.5±178.5) μm vs.(957.5±197.4) μm, P＞0.05], but both were significantly higher than that of the simple plasma group [(499.6±78.0) μm] (P＜0.001). Conclusion The thulium laser + plasma energy transmitted simultaneously by the integrated optoelectrical fiber can vaporize kidney tissue more efficiently without additional thermal damage.

ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.