Moringa oleifera, widely utilized in Ayurvedic medicine, is recognized for its leaves, seeds, and velamen possessing traditional effects such as vātahara(wind alleviation), sirovirecaka(brain clearing), and hridya(mental nourishment). This study aims to identify the medicinal part of ■ in the Sārasvata ghee formulation as described in the Bower Manuscript, while investigating the ameliorative effects of different medicinal parts of M. oleifera on learning and memory deficits in mice and elucidating the underlying molecular mechanisms. A total of 144 male ICR mice were randomly assigned to the following groups: control, model(scopolamine hydrobromide, Sco, 2 mg·kg~(-1)), donepezil(donepezil hydrochloride, Don, 3 mg·kg~(-1)), M. oleifera leaf low-, medium-, and high-dose groups(0.5, 1, 2 g·kg~(-1)), M. oleifera seeds low-, medium-, and high-dose groups(0.25, 0.5, 1 g·kg~(-1)), and M. oleifera velamen low-, medium-, and high-dose groups(0.31, 0.62, 1.24 g·kg~(-1)). Learning and memory abilities were assessed using the passive avoidance test and Morris water maze. Nissl and HE staining were employed to examine histopathological changes in the hippocampus. Transcriptomics and targeted metabolomics were used to screen differential genes and metabolites, with MetaboAnalyst 6.0 and O2PLS methods applied to identify key disease-related targets and pathways. RESULTS:: demonstrated that M. oleifera leaf(1 g·kg~(-1)) significantly ameliorated Sco-induced learning and memory deficits, outperforming M. oleifera seeds(0.25 g·kg~(-1)) and M. oleifera velamen(1.24 g·kg~(-1)). This was evidenced by improved behavioral performance, reversal of neuronal damage, and reduced acetylcholinesterase(AChE) activity. Multi-omics analysis revealed that M. oleifera leaf upregulated Tuba1c gene expression through the synaptic vesicle cycle, enhancing glutamate(Glu), dopamine(DA), and acetylcholine(ACh) release via Tuba1c-Glu associations for neuroprotection. M. oleifera seeds targeted the dopaminergic synapse pathway, promoting memory consolidation through Drd2-ACh associations. M. oleifera velamen was associated with the cocaine addiction pathway, modulating dopamine metabolism via Adora2a-DOPAC, with limited relevance to learning and memory. In conclusion, M. oleifera leaf exhibits superior efficacy and mechanistic advantages over M. oleifera seeds and velamen, suggesting that the ■ in the Sārasvata ghee formulation is likely M. oleifera leaf, providing scientific evidence for its identification in ancient texts.
Animals ; Moringa oleifera/chemistry* ; Male ; Mice ; Seeds/chemistry* ; Plant Leaves/chemistry* ; Mice, Inbred ICR ; Memory Disorders/psychology* ; Transcriptome/drug effects* ; Memory/drug effects* ; Learning/drug effects* ; Metabolomics ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Maze Learning/drug effects*

OBJECTIVES: To investigate the potential circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) immune regulatory network in childhood allergic asthma by analyzing microarray datasets. METHODS: GEO database was used to obtain the datasets of circRNA, miRNA, and mRNA from children with allergic asthma and healthy controls. The Limma package was used to identify differentially expressed circRNA (DEcircRNA), miRNA (DEmiRNA), and mRNA (DEmRNA). ENCORI and other tools were used to predict and construct the regulatory network of endogenous RNA. The DAVID database was used to perform GO and KEGG enrichment analyses, and CIBERSORT and Pearson were used to identify genes associated with immune cell infiltration. RESULTS: A total of 130 DEcircRNAs, 40 DEmiRNAs, and 802 DEmRNAs were identified between the asthma and control groups, and a regulatory network consisting of 12 circRNAs, 7 miRNAs, and 75 mRNAs was established. The GO analysis showed that the differentially expressed genes were mainly involved in the regulation of growth and development, and the KEGG analysis showed that they were mainly involved in the mTOR signaling pathway. The CIBERSORT analysis showed that compared with the control group, the asthma group had higher percentages of CD8⁺ T cells and resting NK cells and lower percentages of resting CD4⁺ memory T cells and activated mast cells. In addition, the Pearson correlation analysis identified six key mRNAs that were positively correlated with immune cell infiltration. CONCLUSIONS The ceRNA immune regulatory network constructed in this study provides a basis for research on the mechanism of childhood allergic asthma and potential therapeutic targets.
Humans ; Asthma/genetics* ; RNA, Circular/physiology* ; MicroRNAs/physiology* ; Child ; Gene Regulatory Networks ; RNA, Messenger/physiology* ; RNA/physiology* ; Male ; Female ; Child, Preschool

OBJECTIVE: To assess the value of the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) score combined with PSA density (PSAD) in the diagnosis of clinically significant prostate cancer (CSPCa) in the PSA grey zone by MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy. METHODS: This retrospective study included 327 male patients with total PSA (tPSA) levels of 4-10 μg/L undergoing MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy in our hospital between January 2021 and December 2023. According to the pathological results, we divided the patients into a CSPCa (n = 44) and a non-CSPCa group (n = 283), collected their clinical and imaging data, and subjected them to statistical analysis. RESULTS: The age, tPSA level, PSAD and PI-RADS score were significantly higher, while the free PSA (fPSA) level, f/tPSA ratio and prostate volume remarkably lower in the CSPCa than in the non-CSPCa group (P<0.05). The areas under the curve (AUCs) of PSAD, PI-RADS score and their combination were 0.772, 0.730 and 0.801, with sensitivities of 63.63%, 70.45% and 72.73%, and specificities of 84.10%, 75.62% and 83.75%, respectively (P<0.01). With PSAD 0.2 μg/(ml·cm3) as the best cut-off value and based on the PI-RADS scores, the patients were divided into two groups for analysis. In the patients with PI-RADS scores 2 and 5, the AUCs were 0.534 and 0.643, with sensitivities of 16.67% and 63.64%, and specificities of 85.14% and 64.29%, with no statistically significant differences (P= 0.784, P= 0.228), and in those with PI-RADS scores 3 and 4, the AUCs were 0.794 and 0.843, with sensitivities of 57.14% and 80.00%, and specificities of 87.14% and 81.82%, with statistically significant differences (P= 0.009, P<0.001). CONCLUSION PI-RADS v2.1 score combined with PSAD can effectively improve the diagnostic efficiency of CSPCa in the PSA grey zone by MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy and serve as a guide for selection of prostate biopsy.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Retrospective Studies ; Prostate-Specific Antigen ; Magnetic Resonance Imaging ; Image-Guided Biopsy ; Prostate/pathology* ; Aged ; Middle Aged

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Objective:To investigate the electron microscopic evaluation results of pre-transplant biopsies of deceased donor kidneys and the corresponding recovery of graft function in recipients after kidney transplantation.Methods:A retrospective analysis was conducted on the clinical data and donor kidney electron microscopy (EM) reports of 196 kidney transplant recipients who underwent pre-implantation kidney biopsies at Renmin Hospital of Wuhan University between October 2020 and June 2023. The ultrastructural pathological features assessed in the pre-transplant kidney biopsy included: the number of glomeruli, the presence of leukocytes and endothelial cells within the glomeruli, the arrangement of capillary loops, abnormalities in podocytes, mesangial cells, mesangial matrix and glomerular basement membrane (GBM), and multilayering of the peritubular capillary basement membrane. Referring to the Mayo Clinic/Renal Pathology Society Consensus Report on the pathological classification, diagnosis, and reporting of glomerulonephritis, the expert consensus on renal biopsy pathology reporting models, and the content of the 2019 Banff Transplant Pathology Meeting, a scoring system was established for ultrastructural pathology of donor kidneys. According to the scores, the recipients were divided into three groups: Group A (total score ≥ 8 points, 94 cases), Group B (total score between 6 and 8 points, 85 cases), and Group C (total score < 6 points, 17 cases). The serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria at postoperative day 1, day 7, month 1, month 3, month 6, and year 1 were compared among the three groups.Results:Among the 196 donor kidneys, EM examination before transplantation showed the following findings: 19 cases (9.7%) had prominent leukocyte infiltration within the glomeruli, 8 cases (4.1%) had mild leukocyte infiltration, and the remaining 169 cases (86.2%) showed no obvious increase in glomerular leukocytes. Glomerular capillary loop collapse or narrowing was seen in 19 cases (9.7%). Endothelial cell proliferation was observed in 32 cases (16.3%). Homogeneous thickening of the GBM (400-900 nm) was present in 82 cases (41.8%). Foot process effacement ranged from partial to diffuse. Podocyte vacuolar degeneration was seen in 62 cases (32.1%), and podocyte swelling in 10 cases (5.1%). Electron-dense deposits in the mesangial area were observed in 9 cases (4.6%). Mild tubular epithelial swelling was present in 6 cases (3.1%). Only 22 cases (11.2%) showed no multilayering of the peritubular capillary basement membrane, while 174 cases (88.8%) showed 2 to 5 layers of multilayering. All donor glomeruli showed irregular capillary loop arrangement, and the renal interstitium showed scattered inflammatory infiltration and varying degrees of collagen fiber deposition. Group C had significantly higher qualitative proteinuria levels at day 7 and month 1 post-transplantation compared with Groups A and B ( P=0.036, 0.004). There were no statistically significant differences in other renal function indicators among the groups (all P>0.05). Conclusions:Pre-transplant electron microscopy of donor kidneys helps in accurately assessing donor kidney quality and identifying subtle pre-existing pathological changes. It can serve as a reference tool for predicting post-transplant functional recovery. Mild ultrastructural abnormalities in donor kidneys have a relatively controllable impact on long-term graft outcomes.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Aim To construct and analyze the genotype of G protein-coupled receptor kinase 2(GRK2)conditional knockout mice in synoviocytes,and to provide an animal model for stud-ying the function of GRK2 in synoviocytes.Methods Grk2flox/+mice were bred to generate Grk2flox/flox mice,Grk2flox/flox mice were bred to Col1a1-iCre+mice,Grk2flox/+Col1a1-iCre+mice were bred to Grk2flox/flox mice.Grk2flox/flox Col1a1-iCre+mice were ob-tained as target mice.DNA was extracted and amplified by PCR to identify the genotype.Western blot was used to verify the effect of Grk2 knockout in synovium,liver and kidney tissues.HE staining was used to detect the effects of Grk2 conditional knockout in synovial cells on ankle synovium,liver and kidney tissues.Multiple immunofluorescence was used to detect GRK2 expression in synovial cells.Results The results of gene iden-tification showed that Grk2flox/flox Col1a1-iCre+mice had both Flox and Col1a1-iCre genotypes.Western blot results showed that GRK2 expression decreased in synovial tissues of Grk2flox/flox Col1a1-iCre+mice,but there was no significant change in the expression of GRK2 in liver and kidney tissues.HE staining showed that Grk2flox/flox Col1a1-iCre+mice had no significant pathological changes in the ankle synovium,liver and kidney.The results of multiple immunofluorescence showed that GRK2 expression in synovial cells of Grk2flox/flox Col1a1-iCre+mice de-creased.Conclusion Grk2 conditional knockout mice in syno-viocytes are successfully constructed and identified,which pro-vides an animal model for further study of the role of GRK2 in synovial-related diseases.

Objective:To quantify thoracic and abdominal movements during breathing using inertial measurement units (IMUs) and to build a machine learning model which identifies the abdominal breathing (AB) pattern.Methods:Ten rehabilitation therapists formed the study′s professional group, while 15 patients receiving AB training comprised the validation group. Two synchronized IMUs were applied to capture breathing motions during natural breathing (NB), deep breathing (DB) and AB. Six kinematic features were extracted from each respiratory cycle, and inter-group and inter-pattern differences were analyzed. Correlation analysis was also performed with manually measured changes in thoracic and abdominal circumferences. A support vector classification model for AB pattern detection was then developed using data from the professional and validation groups.Results:A total of 1113 respiratory cycles were extracted and analyzed. The breathing pattern significantly influenced all of the kinematic features studied (0.21≤partial η 2≤0.65, all P≤0.001). The ranges of the angles in medial-lateral axis of the IMUs showed strong correlation with the changes in abdominal and thoracic circumferences (ρ1=0.928, ρ2=0.807, P≤0.001 in both cases). A greater range of abdominal angles was found during AB compared to the other patterns. The best of the models achieved an F1 score of 0.970 (sensitivity: 0.983, specificity: 0.980) in validation. Conclusions:AB generates the greatest abdominal movement. Combining IMUs and machine learning can provide real-time quantification of chest movement and accurate detection of AB during breathing training.

Objective:To investigate the high-risk factors for early postoperative recurrence in patients with colorectal cancer liver metastasis (CRLM).Methods:The clinical data of 156 CRLM patients who underwent hepatic metastasectomy at the Li Huili Hospital, Ningbo University from Jan 2015 to Dec 2021 was retrospectively analyzed.Results:Among 156 patients, the postoperative recurrence rate was 55.8% (87/156).There were significant differences ( P<0.05) in the primary tumor site, T stage, TBS score, preoperative concentrations of CEA, CA199 and CA125, the maximum diameter of metastatic tumors and the number of metastatic tumors between the group with recurrence in one year and the group without recurrence in one year. Multivariate analysis showed that preoperative CA125 concentration ( OR=1.021, P=0.020), CEA concentration ( OR=1.044, P=0.018), and tumor burden score ( OR=3.067, P=0.011) were high risk factors influencing early recurrence ( P<0.05). In the low TBS score group(≤4), among the 49 patients who underwent simultaneous resection, 13 suffered from recurrence within 1 year, with a recurrence rate of 26.5%. Meanwhile, among the 29 patients who underwent staged resection, 17 suffered from recurrence within 1 year, with a recurrence rate of 58.6% ( P<0.05). In the high TBS score group(>4), among the 51 patients who underwent simultaneous resection, 37 suffered from recurrence within 1 year, with a recurrence rate of 72.5%, while in the 27 patients who underwent staged resection, 20 suffered from recurrence within 1 year, with a recurrence rate of 74.1% ( P>0.05). Conclusions:Preoperative TBS score, preoperative CA125 concentration, and CEA concentration are high-risk factors for postoperative recurrence in patients with colorectal liver metastases, simultaneous resection in patients with a low TBS score can reduce the risk of recurrence within 1 year after surgery.