Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury，so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge，there were 9 cases of self-catheterization，19 cases of intermittent catheterization，22 cases of reflexive voiding，26 cases of long-term catheterization，and 2 cases using urinary collector.At the end of follow-up，there were 15 cases of self-catheterization，8 cases of intermittent catheterization，34 cases of reflexive voiding，14 cases of long-term catheterization，and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ =21.43，P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

To construct a single-cell transcriptomic map of testicular tissue under hypobaric hypoxia exposure and perform diversity analysis of supportive cells, aiming to provide new insights into the mechanisms of reproductive toxicity for future research.

Mammalian teeth,developing inseparable from epithelial-mesenchymal interaction,come in many shapes and the key factors governing tooth morphology deserve to be answered.By merging single-cell RNA sequencing analysis with lineage tracing models,we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+cells within M1.These PRX1+cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation.Deeper into the mechanisms,we have discovered that Wnt5a,bestowed by mesenchymal PRX1+cells,stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway.The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1.Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs.These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

Objective:To investigate the anti-aging and antioxidant effect of the heat shock transcription factor 1 (HSF1) on human retinal pigment epithelial cells.Methods:Two HSF1-deficient ARPE cells (ARPE/Hsf1 -/-) were constructed by using the clustered regularly interspaced short palindromic repeat and associated protein 9 (CRISPR/Cas9) gene editing system and named H8, H9 konckout cell strains.Experiments were operated on the 3 cell strains: wild-type, H8 and H9 cells.The content of reactive oxygen species in ARPE-19 cell was measured by DHE probe staining combined with flow cytometry technology, and the cell cycle was measured by flow cytometry technology.The cell viability at different time points was measured using cell counting kit-8 (CCK-8).Crystal violet staining assay was used to measure the relative ratio of cell survival.SA-β-gal staining assay was used to detect the ratio of ARPE-19 senescent cells.The expressions of HSP70, HSP27, clusterin (CLU), p53, p21 and interleukin (IL)-1β proteins were measured by Western blot technology.The expressions of p53, p21, IL-6, IL-8, IL-1β and monocyte chemoattractant protein 1 (MCP1) mRNA were measured by quantitative real-time PCR technology.Relative expression of heat shock response protein under different heat shock treatment conditions and HSP90 inhibitor IPI504, relative survival with different concentrations of H 2O 2, relative expression of p21 protein after treatment with or without ROS scavenger N-acetylcysteine (NAC) were compared in each cell strain. Results:Gene sequencing showed that H8 and H9 cell strains successfully carried mutated genes.Western blot experiment results showed that H8 and H9 cell strains did not express HSF1 protein, and HSF1 was successfully knocked out in ARPE-19 cells.Compared with wild-type cell, the expression levels of HSP70, HSP27 and CLU proteins in H8 and H9 cell strains significantly decreased, with statistically significant differences (all at P<0.05), and no significant difference was found in the relative HSP90 protein expression level ( F=0.29, P>0.05).Under different heat shock stimulation and IPI504 induction, the HSP70, HSP27, and CLU protein levels significantly increased in wild-type cells compared with before treatment, and the HSP70, HSP27, and CLU protein levels were significantly lower in H8 and H9 cell strains than in corresponding treated wild-type cells (all at P<0.05).Compared with wild-type cell strains, cell viability significantly decreased in H8 and H9 cell strains at 24, 48, 72, and 96 hours (all at P<0.05).Compared with wild-type cell strains, the percentage of cells in G1 phase was significantly higher and the mRNA and protein levels of the cell cycle inhibitors p53 and p21 significantly increased in H8 and H9 strains, showing statistically significant differences (all at P<0.05), and the ratio of positive cells for SA-β-gal staining significantly increased, showing statistically significant differences (all at P<0.001).The relative expression of aging-related inflammatory factors IL-6, IL-8, IL-1β, and MCP1 mRNA decreased, and the differences were statistically significant (all at P<0.001).In addition, compared with wild-type cell strains, the content of reactive oxygen species (ROS) was higher in H8 and H9 cell strains, and the differences were statistically significant (all at P<0.001).The expression of p21 protein in H8 and H9 cell strains wtih NAC treatment decreased significantly compared with non-NAC treatment cells (both at P<0.05).Compared with wild-type cell strains, H8 and H9 cell viability decreased at 200, 400, 600, and 800 μmol/L H 2O 2 treatment conditions, and the differences were statistically significant (all at P<0.05). Conclusions:Knockdown of HSF1 can downregulate the expression of heat shock proteins, activate the ROS/P53/P21 pathway, induce senescence in RPE cells, and increase the sensitivity of RPE to oxidative stress stimuli.HSF1 may have anti-senescence and anti-oxidant regulatory effects in RPE cells.

Objective:To investigate the effects of evidence-based precision nursing in patients with sarcopenia undergoing total knee arthroplasty (TKA) .Methods:By convenience sampling, totally 41 TKA patients with sarcopenia treated in the Department of Orthopedics at The First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were selected as the control group, and 41 TKA patients with sarcopenia treated from March 2022 to March 2023 as the observation group. Patients in the control group received conventional nursing care, while patients in the observation group received an evidence-based precision nursing plan. The differences in muscle mass, grip strength, physical activity ability, knee joint function, and quality of life between the two groups before and after the intervention were compared.Results:After the intervention, the total muscle mass, affected limb skeletal muscle mass, limb skeletal muscle mass, limb skeletal muscle mass index, and grip strength in the observation group were significantly higher than those in the control group ( P< 0.05). The scores on the Short Physical Performance Battery, Lysholm Score, and Sarcopenia Quality of Life Scale in the observation group were also significantly higher than those in the control group ( P<0.05) . Conclusions:Evidence-based precision nursing can improve postoperative muscle mass and strength, enhance physical activity ability and joint function, and improve the quality of life in TKA patients with sarcopenia.

Objective:To screen active antibacterial components from licorice extract using BamA and BamD, the core components of Escherichia coli ( E. coli) β-barrel assembly machinery (BAM), as targets in order to combat the increasingly serious problem of antibiotic resistance. Methods:Affinity ultrafiltration combined with high performance liquid chromatography-mass spectrometry (HPLC-MS) was used to screen the potential components interacting with BamA and BamD from licorice extract. Changes in the expression of bamA and bamD genes of E. coli after treatment with the compounds were detected by fluorescence quantitative PCR, and the effects of the compounds on the function of the BAM complex to integrate outer membrane proteins into the bacterial outer membrane were analyzed using an in vitro recombination system. The influence of the compounds on the integrity of bacterial membranes was evaluated through analyzing the accumulation of SDS within the bacterial cells. Results:Bioaffinity ultrafiltration combined with HPLC-MS screening revealed that 18β-glycyrrhetinic acid could interact with BamD. After 18β-glycyrrhetinic acid treatment, the expression of bamA gene increased by 1.5 times, and the expression of bamD gene increased by 2 times. However, the inhibitory effect of 18β-glycyrrhetinic acid on the membrane insertion function of the BAM complex was not observed in the in vitro recombinant system assay, and the cell membrane integrity assay experiments did not reveal any disruption of the E. coli cell membrane by 18β-glycyrrhetinic acid. Conclusions:Using BamA and BamD proteins as targets, a natural product screening method using affinity ultrafiltration combined with HPLC-MS is established. The screening result shows that 18β-glycyrrhetinic acid can interact with BamD and affect the expression of outer membrane proteins in E. coli. Therefore, the screening and experimental procedures established in this study are of good reference value for the screening of novel antimicrobial drugs from other sources targeting outer membrane proteins, and this study also suggests that the selection of the relevant target sites is crucial for the successful screening of the corresponding natural products.

ObjectiveTo investigate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) combined with robot-assisted therapy on upper limb function of subacute stroke patients. MethodsFrom March, 2022 to March, 2023, 60 subacute stroke patients from Dushu Lake Hospital and the First People's Hospital of Kunshan were randomly divided into control group (n = 20), robot group (n = 20) and combined group (n = 20). All the groups received conventional treatments including medication, physical therapy and occupational therapy; the robot group received sham taVNS combined with hand robot-assisted therapy; while the combined group received taVNS combined with hand robot-assisted therapy, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and hand part, the root mean square (RMS) electromyography of the extensor carpi radialis and extensor digitorum muscles during contraction, and the latency and amplitude of transcranial magnetic stimulation motor-evoked potential (TMS-MEP) before and after treatment. ResultsAfter treatment, the scores of FMA-UE and hand part, RMS of the extensor carpi radialis and extensor digitorum muscles, and latency and amplitude of TMS-MEP improved in all the groups (t > 2.099, P < 0.05); and they were the best in all indicators in the combined group (F > 9.106, P < 0.001). ConclusiontaVNS combined with robot-assisted therapy can promote central nervous system remodeling and further improve upper limb function in stroke patients.

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.
Gene Expression Regulation, Developmental ; Odontogenesis ; Signal Transduction ; Tooth/metabolism* ; Humans

Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1⁺ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1⁺ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1⁺ cells in PDL cells. The behavior of PRX1⁺ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1⁺ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1⁺ cells; during transplanted teeth PDL reconstruction, PRX1⁺ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1⁺ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.
Animals ; Cell Differentiation ; Mesenchymal Stem Cells ; Mice ; Molar ; Osteogenesis/physiology* ; Periodontal Ligament