ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO₂) injection integrating visually identifiable staining and magnetic resonance (MR) T₁/T₂ dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO₂ was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO₂ was directly measured using a pH meter. The osmolality pressure of CN-MnO₂ was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO₂ injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T₁ and T₂ relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R₁ and R₂) and calculate the corresponding relaxivities (r₁ and r₂), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO₂ injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO₂ group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO₂ injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO₂ appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO₂ was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO₂ was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r₁ and r₂ values of 9.6 L·mmol^-1·s^-1 and 17.2 L·mmol^-1·s^-1, respectively, indicating favorable T₁/T₂ contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO₂ showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO₂ group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO₂ group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO₂ injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T₁/T₂ dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.

[Objective]To investigate the mechanism of Wumen Gumibao Decoction in treating senile osteoporosis(SOP)of senescence accelerated mouse prone 6(SAMP6)mice.[Methods]SAM-resistant 1(SAMR1)mice was set as control group,SAMP6 mice were randomly divided into model group(SAMP6),Chinese medicine low dose group(SAMP6+Wumen Gumibao Decoction 7.5 g·kg-1)and Chinese medicine high dose group(SAMP6+Wumen Gumibao Decoction 15.0 g·kg-1),with 10 mice in each group.Mice in control group and model group were gavaged with equal volume of 0.9%sodium chloride solution,and the two groups of Chinese medicine were given Wumen Gumibao Decoction,once a day for 12 weeks.The changes of body mass were observed during the experiment.At the end of the experiment,hematoxylin-eosin(HE)staining was used to observe the pathological changes of the femur in mice.Micro computed tomography(Micro-CT)was used to observe the microstructure and parameters of the femur.The serum levels of calcium(Ca),phosphorus(P)was detected with biochemical method,and the serum levels of calcitonin(CT),procollagen type Ⅰ N-terminal propeptide(PⅠNP),bone γ-carboxyglutamic acid-containing protein(BGP),alkaline phosphatase(ALP),tartrate resistant acid phosphatase(TRACP),procollagen type Ⅰ C-terminal propeptide(PⅠCP),insulin-like growth factor-1(IGF-1),parathyroid hormone(PTH)were detected by enzyme-linked immunosorbent assay(ELISA).Immunohistochemical(IHC)staining was used to detect Wnt3α,phosphorylated-b-catenin(p-b-catenin),osteoprotegerin(OPG),receptor activator of nuclear factor-κB(RANK)and ligand of receptor activator of NF-κB(RANKL),secretory protein Dickkopf-1(DKK1)and glycogen synthase kinase 3b(GSK3b).[Results]Compared with control group,the cortical bone texture,direction and arrangement of bone cells in bone tissue of model group were disordered,and the trabecular structure was loose,showing a state of osteoporosis,bone microstructure parameters bone mineral density,bone volume/tissue volume ratio,trabecular number,trabecular thickness decreased significantly(P<0.05)and trabecular separation increased significantly(P<0.05).The serum levels of Ca,BGP,PⅠNP,CT and ALP were significantly decreased(P<0.05),and P,TRACP,PⅠCP and IGF-1 were significantly increased(P<0.05).In addition,the expression of Wnt3a as significantly down-regulated(P<0.05),and the expression of p-β-catenin,OPG,RANK,RANKL,DKK1 and GSK3β was significantly up-regulated(P<0.05).Compared with model group,Chinese medicine low and high dose groups can improve the pathological morphology of the femur to varying degrees,increase the number of bone trabeculae and reduced the fracture of bone trabeculae,and improved the related parameters of bone microstructure(P<0.05).The levels of serum Ca,CT,BGP,PⅠNP and ALP were increased(P<0.05),and the levels of P,TRACP,PⅠCP and IGF-1 were decreased(P<0.05),and PTH was increased(P<0.05).At the same time,it could up-regulate the expression of Wnt3α protein in the femur(P<0.05)and down-regulate the expression of p-β-catenin,OPG,RANK,RANKL,DKK1 and GSK3b protein(P<0.05).[Conclusion]Wumen Gumibao Decoction has the effect of significantly improving osteoporosis in SAMP6 mice,and its mechanism may be related to its regulation of Wnt/β-catenin and OPG/RANK/RANKL signaling pathways.

[Objective]To investigate the mechanism of Wumen Gumibao Decoction in treating senile osteoporosis(SOP)of senescence accelerated mouse prone 6(SAMP6)mice.[Methods]SAM-resistant 1(SAMR1)mice was set as control group,SAMP6 mice were randomly divided into model group(SAMP6),Chinese medicine low dose group(SAMP6+Wumen Gumibao Decoction 7.5 g·kg-1)and Chinese medicine high dose group(SAMP6+Wumen Gumibao Decoction 15.0 g·kg-1),with 10 mice in each group.Mice in control group and model group were gavaged with equal volume of 0.9%sodium chloride solution,and the two groups of Chinese medicine were given Wumen Gumibao Decoction,once a day for 12 weeks.The changes of body mass were observed during the experiment.At the end of the experiment,hematoxylin-eosin(HE)staining was used to observe the pathological changes of the femur in mice.Micro computed tomography(Micro-CT)was used to observe the microstructure and parameters of the femur.The serum levels of calcium(Ca),phosphorus(P)was detected with biochemical method,and the serum levels of calcitonin(CT),procollagen type Ⅰ N-terminal propeptide(PⅠNP),bone γ-carboxyglutamic acid-containing protein(BGP),alkaline phosphatase(ALP),tartrate resistant acid phosphatase(TRACP),procollagen type Ⅰ C-terminal propeptide(PⅠCP),insulin-like growth factor-1(IGF-1),parathyroid hormone(PTH)were detected by enzyme-linked immunosorbent assay(ELISA).Immunohistochemical(IHC)staining was used to detect Wnt3α,phosphorylated-b-catenin(p-b-catenin),osteoprotegerin(OPG),receptor activator of nuclear factor-κB(RANK)and ligand of receptor activator of NF-κB(RANKL),secretory protein Dickkopf-1(DKK1)and glycogen synthase kinase 3b(GSK3b).[Results]Compared with control group,the cortical bone texture,direction and arrangement of bone cells in bone tissue of model group were disordered,and the trabecular structure was loose,showing a state of osteoporosis,bone microstructure parameters bone mineral density,bone volume/tissue volume ratio,trabecular number,trabecular thickness decreased significantly(P<0.05)and trabecular separation increased significantly(P<0.05).The serum levels of Ca,BGP,PⅠNP,CT and ALP were significantly decreased(P<0.05),and P,TRACP,PⅠCP and IGF-1 were significantly increased(P<0.05).In addition,the expression of Wnt3a as significantly down-regulated(P<0.05),and the expression of p-β-catenin,OPG,RANK,RANKL,DKK1 and GSK3β was significantly up-regulated(P<0.05).Compared with model group,Chinese medicine low and high dose groups can improve the pathological morphology of the femur to varying degrees,increase the number of bone trabeculae and reduced the fracture of bone trabeculae,and improved the related parameters of bone microstructure(P<0.05).The levels of serum Ca,CT,BGP,PⅠNP and ALP were increased(P<0.05),and the levels of P,TRACP,PⅠCP and IGF-1 were decreased(P<0.05),and PTH was increased(P<0.05).At the same time,it could up-regulate the expression of Wnt3α protein in the femur(P<0.05)and down-regulate the expression of p-β-catenin,OPG,RANK,RANKL,DKK1 and GSK3b protein(P<0.05).[Conclusion]Wumen Gumibao Decoction has the effect of significantly improving osteoporosis in SAMP6 mice,and its mechanism may be related to its regulation of Wnt/β-catenin and OPG/RANK/RANKL signaling pathways.

Recently,small nucleolar RNAs(snoRNAs)have transcended the genomic"noise"to emerge as pivotal molecular markers due to their essential roles in tumor progression.Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance.Historically,snoRNA research has concentrated on two classical mechanisms:2'-O-ribose methylation and pseudouridylation.This review specifically summarizes the novel regulatory mecha-nisms and functional patterns of snoRNAs in tumors,encompassing transcriptional,post-transcriptional,and post-translational regulation.We further discuss the synergistic effect between snoRNA host genes(SNHGs)and snoRNAs in tumor progression.More importantly,snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes.Accordingly,we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.