Wilson disease （WD） is one of the few treatable neurogenetic disorders. Currently， Western medicine remains the main treatment method for WD， while since the 1990s， multiple studies conducted by Professor Yang Renmin and his team have shown that traditional Chinese medicine （TCM） also has a favorable therapeutic effect. Based on the principle of low-copper diet for WD， this article systematically elaborates on the advantages， limitations， and key considerations of current Western medicine therapies （pharmacotherapy， liver transplantation， and splenectomy） and reviews the research findings of TCM in China， especially the wide application of Gandou Decoction in clinical practice. Studies have shown that Gandou Decoction can effectively improve neurological symptoms， protect hepatic and renal function， and avoid the adverse drug reactions associated with metal chelating agents， and therefore， it can be used an effective long-term adjuvant therapy for WD. It should be noted that symptoms and signs should be considered in integrated traditional Chinese and Western medicine therapy for WD， and high-copper TCM drugs should be avoided to prevent deterioration.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To evaluate the efficacy of transnasal high-flow humidified oxygen therapy in preventing hypoxemia in pediatric patients undergoing gastroscopy.Methods:In this prospective randomized controlled study, 226 pediatric patients, aged 6-12 yr, with a body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing painless gastroscopy at Women and Children′s Hospital of Qingdao University from February 2022 to August 2023, were selected and divided into 2 groups ( n=113 each) using the simple randomization method: normal nasal cannula oxygen therapy group (group N) and transnasal high-flow humidified oxygen therapy group (group H). Anesthesia was induced with intravenous nalbuphine hydrochloride 0.1 mg/kg and propofol 2 mg/kg, and gastroscopy was performed when the Modified Observer′s Assessment of Alertness/Sedation score reached 1. During the operation, group N inhaled oxygen 5 L/min through the nasal catheter; group H inhaled a mixture of air and oxygen through a transnasal high-flow humidified oxygen therapy system at 2 L·kg -1·min -1 (not exceeding 40 L/min), with FiO 2 of 40%. Primary outcomes were the occurrence of hypoxemia and the lowest SpO 2. Secondary outcomes included the requirement for airway interventions (jaw thrust, mask ventilation, endotracheal intubation) and incidence of adverse events (nasal dryness, laryngospasm, apnea, upper airway obstruction, abdominal distension, nausea and vomiting) and endoscopist′s satisfaction with the procedure. Results:A total of 214 patients finally completed the trial, with 106 in group N and 108 in group H. Compared with group N, the incidence of hypoxemia was significantly decreased (17.9% [19/106] versus 2.8% [3/108]), the lowest SpO 2 was increased, the requirement for jaw lifting interventions was reduced, the incidence of nasal dryness was decreased, and the degree of endoscopist′s satisfaction with the procedure was increased ( P<0.05), and no significant change was found in the other outcomes in group H ( P>0.05). Conclusions:Transnasal high-flow humidified oxygen therapy can effectively prevent hypoxemia and raise the safety of pediatric patients during the gastroscopy.

Objective To observe the effects of auricular point sticking on chronic soft tissue injury of knee joint caused by military training.Methods A total of 77 patients with chronic soft tissue injury of the knee caused by military training admitted to No.901 Hospital of Joint Logistics Support Force from January to November 2022 were enrolled in this study.Auricular point sticking therapy was applied in all the patients.Visual analogue scale(VAS)score,the range of motion of the knees and knee temperature were recorded before and after treatment.Results The VAS score was 6.10±1.23,3.03±0.95,and 2.70±0.93 before treatment,15 min and 24 h after treatment,respectively.The VAS score after treatment were significantly lower than that before treatment(P<0.01).The range of motion of the knees was(79.08±11.59)°,(104.79±8.49)°,and(108.08±9.36)° before treatment,15 min and 24 h after treatment,respectively.The knee flexion after treatment were significantly higher than that before treatment(P<0.01).The knee temperature at 15 min after treatment was significantly higher than that before treatment([30.68±1.38]℃vs.[29.30±1.41]℃,P<0.01).Conclusion Auricular point sticking can reduce the pain of patients with chronic soft tissue injury of the knee and increase the range of joint motion.It is safe and simple and has good compliance.

Objective:To detect the expression of sialylated CD15 (CD15s) in the tumor cells of classical Hodgkin lymphoma using a modified immunohistochemical approach.Methods:From 2009 to 2024, 53 cases of classical Hodgkin lymphoma were collected in the Department of Pathology, Peking University Cancer Hospital, in which 21 cases that were CD15-negative or showed only focal weak positivity were selected. Immunohistochemical staining for CD15 was performed on a Leica automated stainer using three different antibody clones (MMA, Carb3, and IHC527). Tissue sections were digested with sialidase at varying concentrations and incubation times, followed by immunohistochemical staining with the MMA clone. Multiplex immunofluorescence was applied for co-staining of CD15 (MMA) and CD30 (JCM182), and analysis was conducted using APTIME and HALO software.Results:There were 30 male patients and 23 female patients, with an age range of 14 to 73 years and a median age of 32(26,46) years. None of the three CD15 antibody clones significantly improved the CD15 positive rate in the 14 completely negative and 7 weakly positive cases, with no notable differences observed among the clones( P>0.05). After sialidase digestion, tissue morphology remained well-preserved. Optimal CD15 staining was achieved with a 1∶1 diluted sialidase incubated at 37 ℃ for one hour. This treatment significantly enhanced the detection rate of CD15 antigen in Hodgkin Reed-Sternberg cells ( P<0.001). Conclusion:Sialidase digestion effectively unveils sialylated CD15 expression in classical Hodgkin lymphoma, markedly improving its detection in HRS cells.

Objective To investigate the effect of moxibustion on different phenotypic expression of macrophages in rheumatoid arthritis(RA).Methods Thirty rats were randomly divided into the blank group,the model group and the moxibustion group,with 10 rats in each group.Rats in the model group and the moxibustion group were injected with complete Freund's adjuvant(CFA)into right foot pad to prepare RA model.The moxibustion group received moxibustion treatment.The blank group was injected with the same amount of normal saline.The thickness of foot pad was measure and arthritis index score was performed.Pathological changes of joints were observed by hematoxylin eosin staining(HE),and the expressions of CD80,CD163 and SPP1 in macrophages of synovial tissue were detected by immunofluorescence.Results Compared with the blank group,arthritis index score and thickness of foot pad were increased in the model group and the moxibustion group(P＜0.05).After moxibustion treatment,compared with the model group,the score of arthritis index and thickness of foot pad were decreased in the moxibustion group(P＜0.05).HE staining showed joint space narrowing,subchondral bone destruction and inflammatory cell infiltration in the model group.The degree of joint space narrowing,subchondral bone destruction and inflammatory cell infiltration were less in the moxibustion group than those in the model group.Compared with the blank group,the scores of synovial tissue hyperplasia,synovial fibrous tissue hyperplasia and inflammatory cell infiltration increased in the model group.Compared with the model group,scores of synovial tissue hyperplasia,fibrous tissue hyperplasia and inflammatory cell infiltration decreased in the moxibustion group(P＜0.05).Results of immunofluorescence detection showed that compared with the blank group,the expressions of CD80 and SPP1 in synovial tissue were up-regulated in the model group,while the expression of CD163 was down-regulated.Compared with the model group,the expressions of CD80 and SPP1 were down-regulated,and the expression of CD163 was up-regulated in the moxibustion group(P＜0.05).Conclusion Moxibustion can regulate the expression of different phenotypes of macrophages and reduce synovial inflammation of RA.The mechanism may be related to regulating the expression of different phenotypes of macrophages.

Objective:To systematically review and evaluate prediction models for aspiration risk in enteral nutrition patients, providing a reference for the development and application of future models.Methods:Literature related to prediction models for aspiration risk in enteral nutrition patients was searched in China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, Web of Science, Cochrane Library, Embase, and PubMed, with the search period covering from the inception of the databases to August 30, 2024. Two researchers independently conducted literature screening and data extraction, and the PROBAST tool was used to assess the risk of bias and applicability of the included studies.Results:A total of 18 studies were included, involving 24 prediction models, with sample sizes ranging from 103 to 512 and an event rate of 9.46% to 49.87%. The top six predictive variables reported most frequently were baseline age, history of aspiration, length of nasogastric tube insertion, nutritional risk, impaired consciousness, and Acute Physiology and Chronic Health Evaluation-Ⅱscore. The area under the receiver operating characteristic curve of the models ranged from 0.756 to 0.992. Twelve studies reported model calibration, six studies conducted internal validation only, one study conducted external validation only, and four studies performed both internal and external validation. The overall applicability of the 18 studies was good, but the risk of bias was high, mainly due to improper handling of continuous variables and missing data.Conclusions:The aspiration risk prediction models developed in various studies for enteral nutrition patients show good applicability but carry a high risk of bias. Future efforts should focus on further optimizing the model construction process, internal and external validation, and result analysis to provide more reliable and scientific tools for clinical aspiration risk assessment.

Objective:To explore the core factors of self-management and quality of life (QOL) in patients with chronic obstructive pulmonary disease (COPD) and the internal relationship between these two constructs.Methods:A convenience sampling method was used to enroll 210 COPD patients who visited the Fifth Affiliated Hospital, Sun Yat-sen University from January to December 2022. Data were collected using Self-Management Scale and 36-item Short-Form. A relationship network between self-management and QOL was constructed via network analysis, and centrality indicators and network stability were calculated.Results:A total of 210 questionnaires were distributed, and 205 valid questionnaires were recovered, with an effective recovery rate of 97.6%. Emotional management was identified as the core node in both the overall network and the self-management subnetwork (2.064), while vitality was the core node in the QOL subnetwork (0.730). The relationship between self-management and QOL was mainly manifested through the strong association between emotional management and role-emotion.Conclusions:Emotional management is the core factor in the relationship between self-management and QOL in COPD patients. The overall network of self-management and QOL is influenced by the strong association between emotional management and role-emotion.

OBJECTIVES: To elucidate the molecular mechanism by which villin-like protein VILL (VILL) inhibits proliferation of nasopharyngeal carcinoma (NPC) cells. METHODS: Co-immunoprecipitation (CO-IP) assay, mass spectrometry, Western blotting, immunofluorescence staining, and GST pull-down assay were employed to identify and confirm the protein interacting with VILL that had the highest abundance in NPC cell lines. Transgenic experiments were conducted in both NPC cell lines and nude mice to validate the regulatory role of VILL and its target protein in NPC proliferation. Immunohistochemistry was utilized to assess the correlation of the expression levels of VILL and its target protein in clinical tissue specimens of NPC with the clinical features of the patients. RESULTS: In NPC cell lines (HONE1 EBV and S18), VILL was found to interact most abundantly with the E3 ubiquitin ligase LMO7, and both proteins co-localized in the cytoplasm with direct interactions. Overexpression of LMO7 partially counteracted the inhibitory effect of VILL on NPC cell proliferation. The expression of VILL was significantly downregulated in 136 NPC tissue samples compared to 67 non-cancerous nasopharyngeal tissues (P<0.00001) with close correlation with clinical T stage (P=0.04), N stage (P=0.01), and M stage (P=0.013), whereas LMO7 was highly expressed in all the NPC tissues. CONCLUSIONS VILL overexpression inhibits NPC proliferation probably by suppressing the oncogenic function of LMO7.
Nasopharyngeal Neoplasms/metabolism* ; Humans ; LIM Domain Proteins/metabolism* ; Cell Proliferation ; Cell Line, Tumor ; Animals ; Mice ; Nasopharyngeal Carcinoma ; Mice, Nude ; Transcription Factors/metabolism* ; Carcinoma ; Female ; Microfilament Proteins/genetics* ; Male ; Middle Aged

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps