[摘 要] 目的：通过多组学整合分析，解析肠道菌群在胆管癌（CCA）发生发展中的潜在作用机制并识别相关关键基因。方法：基于SRA数据库的16S rRNA测序数据，比较CCA患者与健康对照者的肠道菌群组成；采用孟德尔随机化（MR）分析评估菌群与CCA风险的遗传关联。通过gutMGene和GeneCards数据库获取相关代谢物与基因，进行代谢和功能富集分析。整合GEO单细胞转录组数据（GSE213452），解析肿瘤微环境的细胞组成，重点关注T细胞亚群及其功能状态，并结合TCGA-CHOL数据集验证关键候选基因的表达差异。结果：与健康对照组相比，CCA患者肠道菌群组成发生显著改变，变形菌门下菌群异常富集（LDA > 4）。MR分析进一步证实，肠杆菌目与肠杆菌科的遗传易感性均与CCA风险呈正向关联。代谢通路富集分析提示，菌群相关代谢物主要参与嘌呤代谢及糖酵解/糖异生等通路；功能富集分析显示，相关基因显著富集于NOD样受体、IL-17、Toll样受体及NF-κB信号通路等炎症免疫通路。单细胞转录组分析结果显示，CCA组织中肿瘤细胞比例显著升高（P < 0.05），T细胞比例由20.7%增至39.2%；拟时序分析结果表明，MKI67⁺ T细胞处于分化末期并呈高增殖特征，其差异基因与菌群相关基因存在交集，其中SERPINA1和IFNG表达在肿瘤免疫微环境中显著变化（P < 0.001），可能发挥核心调控作用。TCGA-CHOL数据集验证显示，SERPINA1在CCA肿瘤组织中显著下调（P < 0.001），而IFNG在肿瘤与正常组织间无显著差异（P > 0.05）。结论：肠道菌群失衡（尤其是肠杆菌科异常增殖）可能通过代谢-免疫调控网络促进CCA进展，T细胞功能变化与关键基因（SERPINA1和IFNG）在MKI67+ T细胞中的差异化表达模式密切相关。

low transit constipation （STC） is a common functional intestinal disorder caused by impaired colonic transit function， characterized by reduced bowel movement frequency， hard stools， and difficulty in defecation. The mitogen-activated protein kinase （MAPK） signaling pathway， which mainly includes extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and p38 subtypes， plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine （TCM） intervention.At the mechanistic level， the MAPK signaling pathway promotes the progression of STC through the following links：（1） Activation of p38 upregulates the expression of aquaporin 3 （AQP3）/AQP4 in the colon， leading to excessive reabsorption of water in the intestinal lumen； （2） It forms a positive feedback loop with nuclear factor-κB （NF-κB） to maintain low-grade intestinal inflammation， releases inflammatory factors such as tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and inhibits smooth muscle contraction； （3） Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2， thereby disrupting the mucosal barrier； （4） The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells， neurons， and interstitial cells of Cajal； （5） Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion， ultimately resulting in impaired colonic transit function.At the intervention level， TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent：yin-nourishing formulas （Zengye Chengqi Tang， Tongbian Tang） mainly regulate the ERK/AQP axis； yang-warming formulas （Jichuan Jian） target both ERK/JNK and anti-apoptosis； heat-clearing formulas （Sanren Tang） focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism， inflammation， barrier function， apoptosis， and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets， establish disease-syndrome integrated STC models， and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”， so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

OBJECTIVES: This study investigates independent risk factors for postoperative internal fixation device infection in patients with maxillofacial fractures and proposes an early warning model based on the synthetic minority over-sampling technique (SMOTE) algorithm. METHODS: A total of 1 104 patients who underwent surgical treatment for maxillofacial fractures at Oral and Maxillofacial Surgery Department, Affiliated Hospital of Nantong University from January 2021 to December 2024 were retrospectively analyzed. The patients were divided into two groups based on the presence of postoperative internal fixation device infection: the infection group (27 cases) and non-infection group (1 077 cases). Clinical data from both groups were collected and subjected to statistical analysis. Univariate and binary Logistic regression analysis were used to identify risk factors for postoperative internal fixation device infection in maxillofacial fractures. Subsequently, a Logistic regression model was established, and the dataset was improved based on the SMOTE algorithm to construct an early warning model with the improved dataset. The prediction performance of the models was compared and validated. RESULTS: Among the 1 104 patients who underwent surgical treatment for maxillofacial fractures, 27 cases of postoperative internal fixation device infections were identified, corresponding to an infection rate of 2.45% (27/1 104). Age, diabetes history, fracture severity, and oral hygiene status were all identified as risk factors for postoperative internal fixation device infections in maxillofacial fractures (all P<0.05). The prediction model based on the original data (P1). The prediction model based on the SMOTE algorithm (P2). Receiver operating characteristic (ROC) curve analysis shows that the area under curve (AUC) for the P2 model was 0.882, the P1 model was 0.861, indicating the superior predictive performance of the P2 model. The DeLong test results show that the difference in AUC between the two models was statistically significant (P<0.05). CONCLUSIONS Age, diabetes history, postoperative fracture severity, and oral hygiene status are all risk factors for infections associated with internal fixation devices after maxillofacial fracture surgery. The proposed early warning model demonstrated good predictive performance. Medical professionals can utilize this model to effectively intervene and anticipate infections related to internal fixation devices after maxillofacial fracture surgery.
Humans ; Algorithms ; Retrospective Studies ; Male ; Female ; Fracture Fixation, Internal/instrumentation* ; Risk Factors ; Middle Aged ; Adult ; Logistic Models ; Surgical Wound Infection/epidemiology* ; Aged ; Internal Fixators/adverse effects* ; Maxillofacial Injuries/surgery* ; Adolescent

Most tumor cells and healthy neurons are at rest during G0 phase.Once the cell cycle is abnormally re-entered under certain conditions,the proliferation of tumor cells and the degenerative necrosis of neurons can be initiated.From the perspective of the cell cycle,cancer and central nervous system diseases,two seemingly different disease types,have a common pathogenesis.This type of diseases is named aberrant cell cycle diseases.As a newly discovered microRNA(miR),miR-1976 is closely related to the regulation of the cell cycle.This review summarizes the progress in the research on miR-1976 in cancer and central nervous system diseases,aiming to provide a reference for the clinical application of miR-1976 in aberrant cell cycle diseases in the future.
MicroRNAs/genetics* ; Humans ; Cell Cycle/genetics* ; Neoplasms/genetics* ; Central Nervous System Diseases/genetics*

Angle class Ⅱ malocclusion is often characterized by mandibular retraction and lip incompetence,which affects the patient's lateral appearance and may even lead to upper airway stenosis.It can be classified into dental and skeletal types.For skeletal class Ⅱ malocclusion patients with mandibular retraction during the peak growth period,mandibular anterior guidance with a functional orthodontic appliance is generally considered as the optimal clinical treatment approach.At present,there remains a paucity of clinical reports on the clinical application of bracket-free clear aligners in mandibular anterior guidance,both domestically and internationally.This article presented a case of an adolescent patient with skeletal class Ⅱ malocclusion accompanied with deep overbite treated with bracket-free clear aligner for mandibular anterior guidance in combination with intermaxillary class Ⅱ traction.During the treatment,vertical correction involved anterior intrusion of the anterior teeth to improve the deep overbite,while horizontal correction included maxillary and mandibular expansion to coordinate the width of the dental arches,and asymmetric anterior guidance was used to correct the midline deviation.After 35 months of treatment,the patient's convex facial profile and mandibular retrusion were significantly improved.The subspinale-nasion-supramentale angle(ANB)was decreased from 6.8° to 3.9°,the overbite and overjet were normalized,and the bilateral canine and molar reached a neutral relationship.The mentolabial sulcus depth(Si-LiPg′)and the soft tissue thickness of pogonion to pogonion(Pm-Pm′)were decreased,resulting in a shallower mentolabial sulcus and a more harmonized lateral facial soft tissue profile.The mandibular incisor to mandibular plane angle(IMPA)was decreased from 116.6° to 110.7°,indicating retraction of the lower incisors during mandibular anterior guidance.In conclusion,the orthodontic strategy of mandibular advancement with clear aligners in skeletal class Ⅱ malocclusion patients can avoid excessive overcompensation of the upper and lower anterior teeth and shorten the orthodontic treatment cycle.

Objective:To identify the main components of Huanglian Jiedu Decoction(HLJDD)using ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS),and to explore the potential mechanism of action of HLJDD in the treatment of gouty arthritis(GA)using network pharmacology and molecular docking methods.Methods:We identi-fied the chemical components of HLJDD by combining UPLC-Q-TOF-MS data acquired in both positive and negative ion modes with reference standards,relevant literature,and database searches.We analyzed the potential therapeutic mechanism of HLJDD for GA by using network pharmacology to determine the intersection targets between the active ingredients of HLJDD and GA for further enrich-ment analysis and visual network mapping.The binding affinity of the active ingredients with the intersection targets was validated through molecular docking.Results:A total of 47 components were identified by UPLC-Q-TOF-MS;54 key components of HLJDD for GA treatment and 37 intersection targets were determined by net-work pharmacology;and the top 10 key targets by Degree value were obtained by protein-protein interaction analysis.The Gene On-tology functional enrichment analysis revealed 20 biological pro-cesses,7 cellular components,and 8 molecular functions.The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated 96 GA-related intervention pathways,in which inflammatory signaling pathways such as interleukin-17(IL-17)and tu-mor necrosis factor(TNF)were involved.Molecular docking verified that the key components of HLJDD had high binding affinity with the core targets.Conclusion:The identified key components in HLJDD,such as phellodendrine,coptisine,wogonin,and β-sitosterol,may alleviate GA by regulating multiple core targets in the IL-17 and TNF pathways,such as PTSG2,which provides a theoretical ba-sis for future investigation into the mechanism of action of HLJDD.

ObjectiveTo analyze the impact of maternal postpartum depression (PPD) at 2 months postpartum on caregiving for infants aged2 to 24 months, and to provide a scientific basis for future maternal and infant healthcare services. MethodsBased on the Shanghai Maternal-Child Pairs Cohort, 1 060 mother-child pairs were selected from those fully participating in follow-up visits at 2, 6, 12, and 24 months postpartum. Pregnancy and childbirth-related information was collected using standardized questionnaire surveys and hospital obstetric and maternity records. The Edinburgh postpartum depression scale was used to assess the maternal postpartum depressive symptoms at 2 months postpartum. At 2, 6, 12, and 24 months postpartum, questionnaire survey was used to evaluate the maternal responsiveness in caregiving and the provision of early learning opportunities for infants. Scores for responsive caregiving and early learning opportunities at 2, 6, 12, and 24 months were grouped based on the 25th percentile (P₂₅) of total scores. The mixed-effects model was used to analyze the longitudinal impact of maternal postpartum depression at 2 months on the caregiving of 2 to 24-month-old infants. ResultsThe longitudinal results from the mixed-effects model did not show an impact of maternal PPD on infant responsive caregiving within 12 months and early learning opportunities within24 months. However, cross-sectional analysis revealed that, compared to the non-PPD group, the risk of low responsive caregiving at 2 months in the PPD group was 93% higher (OR=1.931, 95%CI: 1.113‒3.364, P=0.019). The risks for low provision of early learning opportunities at2 months and 24 months increased by 59% (OR=1.589, 95%CI: 1.082‒2.324, P=0.017) and 60% (OR=1.598, 95%CI:1.120‒2.279, P=0.010), respectively. ConclusionMaternal postpartum depression increases the risk of low responsive caregiving at 2 months, but its long-term effects warrant further research.