Wilson disease （WD） is an autosomal recessive disorder of copper metabolism， and decoppering therapy and symptomatic treatment are the main Western medicine therapies for WD. This article systematically reviews the understanding of the etiology and pathogenesis of WD in traditional Chinese medicine （TCM） and points out that abnormal natural endowment is the core etiology and pathogenesis of WD， with internal accumulation of copper toxicity as the manifestation， liver/spleen/kidney dysfunction as the root cause， and intermingled “toxin， stasis， phlegm， and deficiency” as the key pathogenesis. Literature research and clinical observation are conducted to summarize the common TCM syndromes of WD， including stagnation of liver Qi， internal retention of damp-heat， phlegm-stasis-heat accumulation syndrome， liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency， and syndrome of deficiency damage and phlegm stasis. This article proposes the corresponding therapies and representative prescriptions for each syndrome and discusses the advantages of treatment by stage and integrated traditional Chinese and Western medicine therapy. This article aims to provide a systematic reference for the syndrome differentiation-based treatment of WD in clinical practice of TCM， thereby giving full play to the advantages of TCM in the treatment of this disease.

Cholangiocarcinoma (CCA) is a malignancy characterized by tumor cells originating in the liver or bile ducts, exhibiting features of cholangiocyte differentiation. It poses a significant clinical challenge due to the limited diagnostic and therapeutic options available. Robust animal models are essential for advancing our understanding of CCA pathogenesis and developing effective treatments. This review provides a comprehensive overview of CCA mouse models, highlighting various approaches, including chemical induction, genetically engineered models, and tumor xenografts. Each model is discussed in terms of its establishment techniques, pathological characteristics, and research significance, with a focus on intrahepatic CCA. Chemical induction models, such as diethylnitrosamine- and azoxymethane-induced models, offer insights into tumorigenesis processes, whereas genetically modified models involving alterations in key genes such as Kirsten rat sarcoma viral oncogene homolog, tumor protein 53, and isocitrate dehydrogenase serve as important tools for studying the molecular mechanisms underlying CCA. Xenograft models, including patient-derived xenografts, bridge the gap between experimental research and clinical applications, allowing for precise therapeutic evaluations. By comparing these models, this review underscores their respective advantages and limitations, paving the way for future studies aiming to optimize and innovate CCA modeling strategies.

Objective:To correlate serum bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein (COMP) levels with joint function and systemic inflammatory response in patients with knee osteoarthritis (KOA) complicated by cartilage injury.Methods:This study is a retrospective analysis. It selected 258 patients with knee osteoarthritis who were treated at Yantai Yuhuangding Hospital from January 2022 to December 2023. All patients underwent arthroscopic examination. Based on the presence of cartilage injury, 118 patients with cartilage injury were included in the Group A, while 140 patients without cartilage injury were included in the Group B. Joint function (WOMAC Osteoarthritis Index, Lysholm Knee Function Score), serum levels of BMP-2 and COMP, and systemic inflammatory responses [levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α)] were compared between the two groups. Receiver Operating Characteristic (ROC) curves were drawn to analyze the diagnostic efficacy of serum BMP-2 and COMP levels for KOA complicated by cartilage injury. Pearson correlation analysis was used to assess the correlation between the aforementioned serum markers and the patients' WOMAC Osteoarthritis Index, Lysholm Knee Function Score, as well as serum levels of IL-1, IL-6, and TNF-α.Results:Group A had significantly lower serum BMP-2 levels and Lysholm Knee Function Scores compared with Group B [(9.18 ± 1.65) ng/L vs. (11.43 ± 2.51) ng/L, t = 8.34, P < 0.001; (80.06 ± 8.34) vs. (86.94 ± 7.21), t = 7.11, P < 0.001]. Group A exhibited higher serum levels of COMP, IL-1, IL-6, and TNF-α, as well as a higher WOMAC Osteoarthritis Index, with all differences being statistically significant [(6.88 ± 2.34) μg/L vs. (5.04 ± 1.01) μg/L, t = -8.34, P < 0.001; (43.18 ± 7.81) ng/L vs. (35.96 ± 5.02) ng/L, t = -8.96, P < 0.001; (34.03 ± 6.68) ng/L vs. (28.75 ± 5.61) ng/L, t = -6.90, P < 0.001; (13.17 ± 1.89) ng/L vs. (11.24 ± 1.01) ng/L, t = -10.44, P < 0.001; (137.18 ± 18.95) vs. (121.14 ± 13.58), t = -7.90, P < 0.001]. ROC curve analysis indicated that the area under the curve values for serum BMP-2 and COMP levels in diagnosing KOA complicated by cartilage injury were 0.773 and 0.811, respectively. Pearson correlation analysis revealed a negative correlation between serum BMP-2 levels and the WOMAC Osteoarthritis Index, as well as serum levels of IL-1, IL-6, and TNF-α ( r = -0.52, -0.42, -0.40, -0.57, all P < 0.05). Additionally, serum BMP-2 levels showed a positive correlation with the Lysholm Knee Function Score ( r = 0.51, P < 0.05). Serum COMP levels and the WOMAC Osteoarthritis Index were positively correlated with serum IL-1, IL-6, and TNF-α levels ( r = 0.48, 0.45, 0.37, 0.54, all P < 0.05) and were negatively correlated with the Lysholm Knee Function Score ( r = -0.51, P < 0.05). Conclusions:Serum BMP-2 and COMP levels have certain diagnostic value in patients with KOA complicated by cartilage injury. Moreover, these indicators are correlated with joint function and systemic inflammatory responses. Therefore, they hold promise as potential indicators for assessing disease progression in patients with KOA.

Objective:To investigate the predictive value of transabdominal uterine electromyography for pre-term labor after tocolysis in women with threatened preterm labor.Methods:A total of 48 pregnant women at 28-34 weeks of gestation diagnosed with threatened preterm labor and admitted to The Fourth Affiliated Hospital of Soo-chow University from January to September 2023 were included.According to the response to tocolysis and whether the pregnancy was prolonged for at least 48 h,women were divided into two groups:non-preterm birth within 48 h(n=35)and preterm birth within 48 h(n=13).Uterine electromyography parameters and difference were compared before and after tocolytic therapy in two groups.Univariate Logistic regression was performed to predict the related factors of preterm birth within 48 h after the using of tocolysis in pregnant women with threat-ened preterm birth by uterine electromyography,and receiver operating characteristic(ROC)curve was per-formed to evaluate their performance.Results:Compared to before treatment with tocolysis,after therapy,in the non-preterm birth within 48 h group,significant reductions in contraction frequency,area,duration and amplitude were observed(P<0.05).In the preterm birth within 48 h group,only contraction frequency decreased significant-ly(P<0.05).Univariate Logistic regression indicated that contraction frequency,contraction duration,and contrac-tion area were predictive factors for premature birth within 48 h after tocolysis(P<0.05).When the duration of u-terine contractions lasting for 104.55 s or more the sensitivity and specificity of predicting premature birth within 48 h are 92.3％and 68.6％,respectively.Conclusions:Uterine electromyography may predict the premature birth within 48 h after tocolytic treatment in preterm labor,which may provide reference for subsequent corticosteroid therapy or transfer of high-risk pregnant patients.

Objective:To explore the effects of magnolol on autophagy in intestinal Cajal cells and intestinal motility in rats with acute necrotizing pancreatitis (ANP).Methods:Forty-five Wistar rats were randomly divided into three groups by a random number table: control group, ANP group and magnolol intervention group, with 15 rats in each group. The ANP model was established by intraperitoneal injection of cerulein. The magnolol intervention group received a tail vein injection of 20 μg/kg magnolol ethanol solution 30 minutes after modeling. After 12 hours, ileal tissues were collected for pathological examination and scoring. Intestinal transit rate was measured using the carbon powder propulsion method, and isolated intestinal muscle strips were prepared to assess amplitude and frequency of spontaneous contraction. Oxidative stress markers in intestinal tissues, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels, were measured using xanthine oxidase, thiobarbituric acid, and enzymatic reduction assay kits, respectively. Cajal cells were isolated from intestinal smooth muscle tissues, and the expression of autophagy-related proteins (Beclin1, LC3Ⅱ, LC3Ⅰ, p62) and p-Kit was detected by Western blot. Double immunofluorescence staining was used to trace autophagy in Cajal cells.Results:The pathological scores of ileal tissues in the control, ANP, and magnolol intervention groups were (0.33±0.52), (4.83±0.41), and (3.50±0.55), respectively. The score in ANP group was significantly higher than that in the control group, while the score in the magnolol intervention group was lower than that in the ANP group, with statistically significant differences (all P value <0.05). Intestinal transit rate, amplitude and frequency of spontaneous contraction in the ANP group were significantly slower than those in the control group, while these parameters in the magnolol intervention group were significantly improved compared to the ANP group, with statistically significant differences (all P value <0.05). SOD activity in the control, ANP, and magnolol intervention groups were (73.8±8.1), (42.8±7.2), and (71.2±10.4) N/mg prot, respectively; NO levels were (1.72±0.26), (3.19±0.43), and (1.94±0.23) μmol/g prot; and MDA levels were (1.15±0.38), (3.84±0.30), and (1.68±0.33) nmol/mg prot. SOD activity in the ANP group was significantly lower than that in the control group, while NO and MDA contents were significantly higher. In the magnolol intervention group, SOD activity was significantly higher, and NO and MDA contents were significantly lower than those in the ANP group, with statistically significant differences (all P value <0.01). The levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit in the intestinal Cajal cells of ANP group were significantly higher than those in the intestinal Cajal cells of control group, while the p62 level was significantly lower. In the intestinal Cajal cells of magnolol intervention group, the levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit were significantly lower while the p62 level was significantly higher than those in the intestinal Cajal cells of ANP group, with statistically significant differences (all P value <0.01). The numbers of c-Kit/GFP-LC3 double-positive Cajal cells in the control group, ANP group, and magnolol intervention group were (9.59±5.06), (11.27±8.30), and (10.27±6.30), respectively. The ANP group had significantly more double-positive cells than the control group, while the magnolol intervention group had significantly less double-positive cells than the ANP group, with statistically significant differences (all P value <0.05). Conclusions:Excessive oxidative stress and autophagy in Cajal cells are important mechanisms underlying ANP-induced intestinal motility dysfunction. Magnolol can improve intestinal motility in ANP by antagonizing oxidative stress and reducing autophagy in Cajal cells. p-Kit may play a regulatory role in this process.

OBJECTIVE To study the efficacy of Tianjiang xueshuantong pills in the treatment of coronary heart disease. METHODS In accordance with the common pathogenesis of coronary heart disease， acute myocardial ischemia model， hyperlipidemia model， blood stasis model， and carotid artery thrombosis model were established using Wistar rats or SD rats as the experimental subjects. The effects of Tianjiang xueshuantong pills administered at high， medium， and low doses （0.6， 1.2 and 2.4 g/kg） on hemodynamic parameters and myocardial enzyme markers [lactate dehydrogenase （LDH）， creatine kinase-MB （CK- MB）]， oxidative stress factors [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）]， inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， intercellular adhesion molecule-1 （ICAM-1）]， myocardial infarction percentage， serum lipid indexes [total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， platelet aggregation function 话：022-84845240。E-mail：jiangx@tjipr.com [maximum aggregation rate （MAR）]， and thrombus formation indexes [thrombosis time， thrombus mass， thrombus protein content， plasminogen activator inhibitor-1 （PAI-1）， and tissue-type plasminogen activator （t-PA）] were evaluated in the rat models. RESULTS In myocardial ischemia tests， Tianjiang xueshuantong pills significantly reduced the percentage of myocardial infarction and the levels of CK-MB， LDH， MDA， GSH， IL-6， TNF-α， IL- 1β， and MCP-1 in serum （P＜0.05 or P＜0.01）. In hyperlipidemia tests， high dose of Tianjiang xueshuantong pills significantly reduced the serum levels of TC， LDL and significantly increased the level of HDL in rats after 2 weeks and 4 weeks of administration. In blood stasis tests， different doses of Tianjiang xueshuantong pills significantly reduced MAR of rats （P＜0.01）. In artery thrombosis tests， high dose of Tianjiang xueshuantong pills significantly prolonged the time of thrombosis formation （P＜ 0.01）， significantly reduced the weight and protein content of thrombus and the level of PAI-1 in serum （P＜0.01）. CONCLUSIONS Tianjiang xueshuantong pills exert therapeutic effects on coronary heart disease through multi-dimensional synergistic actions， including anti-myocardial ischemia， lipid-lowering， and anti-thrombotic effects.

Objective:To summarize the current status of the application of automated interactive voice response systems (AIVRS) in post-diagnosis management of chronic disease patients.Methods:A computer search was conducted in PubMed, Embase, Web of Science, CINAHL, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, and VIP, covering the literature from establishing these databases to May 25, 2024. Two researchers screened the literature and extracted data based on inclusion and exclusion criteria.Results:A total of 16 articles were included. The content of AIVRS in post-diagnosis management of chronic disease patients mainly includes self-care guidance, medication management, and decision support. The outcome indicators primarily focus on feasibility evaluation and effect evaluation.Conclusions:AIVRS is feasible in post-diagnosis management of chronic disease patients. However, there are still shortcomings, such as technical limitations, performance issues, and the use of unimodal data to assess patient outcome indicators. Future research could strengthen the theoretical foundation of AIVRS in post-diagnosis management interventions, appropriately add interactive modules, and provide real-time guidance to improve the effectiveness of AIVRS in post-diagnosis management.

Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

Objective:To summarize the experience of designing hair transplantation for post-cleft lip repair moustache defects based on the morphological and tissue characteristics of the upper lip.Methods:A retrospective analysis was conducted on the clinical data of male patients treated at the Hair Transplantation Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 2011 to July 2024. Based on the morphology and tissue texture of the upper lip after cleft lip repair, the position and shape of the moustache were designed. Hair follicles were harvested from the mid-occipital region and/or the jaw shadow area using either the strip harvesting method or the follicular unit excision (FUE) technique. Needles of 21 or 22 gauge were used to create incisions in the recipient sites down to the superficial subcutaneous layer. The hair shafts were clamped with micro-forceps and then transplanted into the recipient sites to restore the moustache shape. Postoperatively, the density, shape, direction of the moustache, and the condition of the donor site scars were observed and followed up.Results:A total of 47 male patients, aged 23-43 years (mean 28.7 years), were included. Among them, 29 had undergone lower triangular flap repair, 13 received the Millard technique, and 5 were treated with other surgical methods for cleft lip repair. For hair follicle extraction, the strip method was used in 7 cases, and FUE in 40 cases. The donor sites included the jaw shadow area (9 cases), mid-occipital region (23 cases), and a combination of both (15 cases). The number of transplanted follicular units ranged from 33 to 500 (mean 217). Follow-up duration ranged from 9 months to 10 years (mean 3.5 years). Postoperative complications included folliculitis in 6 cases, and 4 cases required additional transplantation due to insufficient density after one year. The remaining patients exhibited satisfactory hair growth, with natural mustache shape and direction. The graft survival rate was approximately 80%, and donor site scarring was minimal.Conclusion:When performing hair transplantation to treat post-cleft lip repair moustache defects, the design should prioritize the morphological and tissue characteristics of the upper lip, followed by consideration of overall position and bilateral symmetry of the moustache. Only by fully considering the characteristics of the recipient area can optimally repair outcomes be achieved.

Objective:To establish and optimize a novel method, focus forming assay (FFA), for quantitation of influenza A virus (FluA) and compare its application performance with traditional plague forming assay (PFA).Methods:The foci chromogenic effects of three peroxidase substrates in immunostaining were compared. The PFA and FFA methods were used to explore FluA incubation times and plaque morphology on 12-well plates, and to determine optimal incubation times and virus adsorption volumes for different FluA subtypes on 96-well plates. The correlation between FFA and PFA was evaluated, and the optimized FFA was applied to the in vitro antiviral efficacy analysis of Favipiravir and neutralization test against different subtypes of FluA. Results:TRUEBLUE substrate was identified as the optimal substrate for foci visualization. Compared with the PFA, the FFA showed improved sensitivity and reduced detection time in FluA titration, and good correlation was shown between the two methods′ results. By replacing the 96-well plate with the 12-well plate for FFA titration of different subtypes of FluA, the detection time was shortened, and the amount of serum samples used could be further reduced by optimizing the virus adsorption volume. The half-maximal effective concentration of favipiravir against influenza viruses assessed by the FFA and PFA methods showed no significant difference, and was consistent with the results obtained from quantitative PCR. Additionally, the focus reduction neutralization test and hemagglutination inhibition assays demonstrated strong correlation in determining antibody titers against FluA in serum neutralization assays.Conclusions:The improved FFA method developed here provides a more efficient experimental tool for FluA titration, antiviral drug screening and broad-spectrum vaccine evaluation.