[摘 要] 目的：探讨高良姜素（Gal）调控AMPK/mTOR/ULK1信号通路对胃癌细胞凋亡和自噬的影响及其机制。方法：将胃癌NCI-N87细胞分为对照组、多索吗啡（DM）组、Gal低剂量（Gal-L）组、Gal高剂量（Gal-H）组、Gal-H + DM组。采用MTT法、流式细胞术、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，WB法检测PCNA、C-caspase-3、免疫逃逸相关蛋白（B7H1）、EMT和AMPK/mTOR/ULK1信号通路蛋白的表达水平。建立裸鼠NCI-N87细胞移植瘤模型，观察Gal和5-FU对移植瘤的抑制效果。结果：与对照组比较，DM组NCI-N87细胞增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著升高（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著降低（均P < 0.05）；Gal-L组和Gal-H组NCI-N87细胞的增殖活性、划痕愈合率和侵袭细胞数、N-cadherin、vimentin、PCNA、B7H1、p62和p-mTOR/mTOR蛋白表达均显著降低（均P < 0.05），细胞凋亡率、C-caspase-3、E-cadherin、LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1蛋白表达均显著升高（均P < 0.05）；DM可部分逆转Gal对NCI-N87细胞恶性生物学行为的抑制作用（P < 0.05）；与对照组比较，Gal组和5-FU组裸鼠移植瘤体积和质量均显著降低，肿瘤组织细胞凋亡率显著升高（P < 0.05）。结论：Gal可促进胃癌NCI-N87细胞自噬和凋亡，抑制其增殖、迁移和侵袭，可能与激活AMPK/mTOR/ULK1信号通路有关。

OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed， Embase， Web of Science， CBM， VIP， Chinese Medical Journal Data， Wanfang Data， and CNKI， as well as the official websites of GIN， NICE， Medlive， AHRQ， CSCO， ASCO， and NCCN. The search period was from the establishment of the databases/websites to March 10， 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows： scope and purpose of 85.07%， participants of 47.92%， rigor of development of 57.49%， clarity of presentation of 88.02%， applicability of 8.20%， and independence of 53.39%. Among them， 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants， rigor of development， and independence of the guidelines/consensuses in China were significantly lower than foreign countries （P＜0.05）； the scores for participants and rigor of development of the guidelines were significantly higher than consensuses （P＜0.05）. The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients；platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients； non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants， rigor of development， and independence， to recommend treatment plans based on the different stages of ovarian cancer， and develop guidelines/consensuses that align with China’s national conditions.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Objective:To investigate the molecular characteristics and clinical heterogeneity of Usher syndrome（USH） -related gene variants in patients with hereditary hearing loss in southwest China, providing a basis for early diagnosis and clinical management. Methods:Thirteen patients from twelve families with hearing loss who attended the Affiliated Children's Hospital of Kunming Medical University between January 2017 and March 2021 were enrolled. All patients were identified as carrying USH-related gene variants through next-generation sequencing. Sanger sequencing was performed for all patients and their parents to validate the pathogenic variants. Comprehensive clinical evaluations, including medical history collection, otologic and ophthalmologic examinations, and vestibular function assessments, were conducted. Results:Among the 13 patients, 4 were diagnosed with USH type 1 and 2 with USH type 2. A total of 19 pathogenic or likely pathogenic variants were detected in USH-related genes, including MYO7A,CDH23,USH1C, and USH2A. The causative gene was MYO7A in 3 probands, CDH23 in 5, USH1C in 3, and USH2Ain 2. All patients exhibited an autosomal recessive inheritance pattern. Vestibular dysfunction was observed in 4 patients, and retinitis pigmentosa（RP） in 3 patients. Based on the genotype-phenotype correlation, 6 patients were initially diagnosed with USH, while 7 were classified as having non-syndromic hearing loss（NSHL）. Conclusion:This study revealed the clinical heterogeneity of USH-related gene variants in patients with hereditary deafness in southwest China. Although the clinical manifestations of USH are complex and there are overlapping characteristics between different subtypes, genetic testing provides an important basis for early diagnosis and precise clinical management. Especially for those with typical hearing loss, early genetic diagnosis can provide a window of time for early detection and intervention of retinitis pigmentosa.
Humans ; Usher Syndromes/genetics* ; Myosin VIIa ; Phenotype ; Male ; Female ; Myosins/genetics* ; Mutation ; Cadherins/genetics* ; Child ; Extracellular Matrix Proteins/genetics* ; Adolescent ; Pedigree ; High-Throughput Nucleotide Sequencing ; Cadherin Related Proteins ; Cytoskeletal Proteins ; Cell Cycle Proteins

[摘 要] 目的：探究包被蛋白复合体β1亚基（COPB1）在食管鳞状细胞癌（ESCC）中的表达，及其对ESCC细胞恶性生物学行为的影响、作用机制及临床意义。方法：采用2014～2018年间在河北医科大学第四医院生物样本库中82例ESCC组织及癌旁组织，常规培养正常食管鳞状上皮细胞HEEC和食管癌细胞KYSE-150、KYSE-170、Eca109、TE1、KYSE-30、KYSE-450，用转染试剂将pcDNA3.1-vector（空载体）、pcDNA3.1-COPB1载体，si-NC和si-COPB1转染至KYSE-150、TE1细胞中，记为NC、COPB1-OE、si-NC和si-COPB1组。用数据库数据分析COPB1 mRNA在泛癌组织中的表达及其表达与免疫细胞浸润的关系，qPCR法检测ESCC组织和细胞中COPB1、PIK3CB、CD68、CD163、CD206、ARG1、IL-10 mRNA水平表达情况，WB法检测ESCC组织和各组细胞中的COPB1、PI3K、CD68、CD163、CD206、p-AKT蛋白表达，克隆形成实验和MTS实验检测各组细胞的增殖能力，划痕愈合实验和Transwell实验检测各组细胞的迁移和侵袭能力，免疫组织化学染色（IHC）法检测ESCC组织中COPB1和CD206蛋白表达。以人单核细胞白血病细胞（THP-1）构建巨噬细胞模型，用佛波酯（PMA）和IL-3和IL-4和ESCC细胞上清液诱导巨噬细胞转型，用qPCR和WB法检测CD68和CD206m RNA和蛋白的表达。结果：COPB1在泛癌组织和ESCC组织中均呈高表达且与淋巴结转移和TNM分期有关联（均P < 0.01），COPB1高表达的ESCC患者总生存期短（P < 0.05），COPB1是潜在的ESCC的诊断标志物。COPB1在KYSE-150和TE1细胞中也呈高表达（均P < 0.05），过表达或敲减COPB1可明显抑制或促进KYSE-150和TE1细胞的增殖能力、迁移和侵袭能力（均P < 0.05）。COPB1表达变化诱导的差异表达基因主要富集于PI3K/AKT通路（均P < 0.001）, COPB1可促进PI3K/AKT通路的活化（P < 0.05），COPB1高表达可导致M2型巨噬细胞浸润增加（P < 0.05），COPB1高表达促进TAM/M2极化（P < 0.05）。结论：COPB1在ESCC组织中呈高表达，其可激活PI3K/AKT通路及调控肿瘤免疫微环境促进 ESCC发生发展，COPB1有望成为ESCC诊断和预后的生物标志物及治疗靶点。

Objective To evaluate the effect of dapagliflozin on myocardial function in early spontaneously hypertensive rats(SHR)with layer-specific global longitudinal strain(GLS).Methods A total of 45 male SHR aged 6 weeks were randomly divided into control group(normal saline),dapagliflozin group[1 mg/(kg·day)],and losartan group[10 mg/(kg·day)].Fifteen male Wistar-Kyoto(WKY)rats at same age with normal blood pressure were subjected and served as blank control group.During 8 weeks of intervention,systolic blood pressure(SBP)was measured,and conventional echocardiography and two-dimensional speckle tracking echocardiography(2DSTE)were performed and the results were collected to acquire the longitudinal strain of each layer of left ventricular(LV)myocardium.The parameters were compared among the groups.The pathological changes of myocardium were observed in each group of rats.Results Compared with the WKY group,LV ejection fraction(LVEF)and LV fraction shortening(LVFS)at week 8 were decreased in the control group(P＜0.05),but no such decreases were observed in the dapagliflozin group and the losartan group.The GLS of endo-myocardium(GLSendo)at the 6th week was decreased,and GLSendo,GLSmid and GLSepi at the 8th week were all decreased in the control group than the WKY group(all P＜0.05).But there were no statistical differences in the above 3 indicators in the dapagliflozin and losartan groups when compared with the WKY group(all P＞0.05).The pathological results showed that myocardial interstitial fibrosis was observed in the control group at the 6th week.Conclusion Dapagliflozin can effectively improve myocardial function in early SHR.

Objective To explore the value of preoperative ultrasound examination in the prediction of restenosis of arteriovenous fistula(AVF)after percutaneous transluminal angioplasty(PTA)in hemodialysis patients.Methods A case-control trial was conducted on 225 hemodialysis patients who undergoing PTA due to AVF in our hospital January 2023 to May 2024.After 3 months of follow-up,they were divided into a patency group(n=204)and a restenosis group(n=21)according to the occurrence of postoperative restenosis.The preoperative clinical data and ultrasound parameters were compared between the groups.Binary logistic regression analysis was used to identify the independent factors for AVF restenosis after PTA.Receiver operating characteristic(ROC)curve was drawn to evaluate the value of preoperative stenosis length in the prediction of the restenosis after PTA.Results There were significant differences in preoperative internal diameter at the site of stenosis,stenosis length,stenosis number,intimal thickness,and brachial artery flow between the 2 groups(P<0.05).Preoperative stenosis length(OR=1.856,95%CI:1.350～2.552,P<0.001)was an independent factor of AVF restenosis in hemodialysis patients after PTA.ROC curve analysis showed that the area under the curve of preoperative stenosis length in predicting restenosis after PTA was 0.868(95%CI:0.784～0.953,P<0.001),with a sensibility and specificity of 85.7%and 80.4%,respectively.Conclusion Preoperative stenosis length may be an independent factor for AVF restenosis after PTA in hemodialysis patients.

Objective To objectively evaluate the clinical efficacy and safety of acupuncture in regulating the mood of patients with post-stroke depression(PSD)and explore the possible target of acupuncture intervention.Methods 76 patients with PSD were randomly divided into treatment group and control group.The control group was treated with routine treatment measures for stroke,and the treatment group was treated with acupuncture on this basis.The main acupoints were Shangxing,Baihui,Shenting,Fengchi and Dugu,supplemented by acupuncture on Taichong,Hegu,Quchi,Neiguan,Yanglingquan,Zusanli and Taixi,5 times a week,continuously treated for 4 weeks,followed up on the 90th day after treatment.The levels of serum 5-hydroxytryptamine,norepinephrine and intestinal microflora before and after treatment were compared with the 17 Hamilton Depression Scale scores(HAMD),modified Barthel Index(MBI),and the levels of serum 5-hydroxytryptamine and norepinephrine before and after treatment.Results The HAMD score and MBI index of the two groups after treatment and follow-up were lower than those before treatment.The levels of 5-hydroxytryptamine and norepinephrine in the treatment group after treatment were higher than those before treatment(P<0.01),and significantly higher than those in the control group(P<0.01).After acupuncture,the dominant bacterial groups of Bacteroides,Thick-wall bacteria and Broughter bacteria in patients showed an upward trend(P>0.05).The difference of bacteria before and after treatment was mainly concentrated in signal pathways such as ECM-receptor interaction,and the difference was statistically significant(P<0.01).Conclusion Acupuncture can help patients improve their ability of daily living,and also improve the relative abundance of intestinal flora in PSD patients to a certain extent,so as to regulate the levels of 5-HT and NE to relieve the depression of patients,which is worthy of promotion in clinical practice.

Purpose: The objective of this study was to evaluate the diagnostic value of transvaginal contrastenhanced ultrasound (CEUS) in differentiating benign from malignant endometrial lesions and assessing the extent of myometrial invasion. Methods: A total of 70 patients who underwent surgery for endometrial lesions at the authors’ hospital were selected. Transvaginal ultrasound examination and CEUS were performed for quantitative and qualitative analysis. Based on the CEUS results, an International Federation of Gynecology and Obstetrics (FIGO) disease grade was assigned and compared with pathological findings. Results: Postmenopausal vaginal bleeding is a key clinical manifestation of endometrial carcinoma. Among the patients with endometrial carcinoma, compared with normal myometrium, the lesion areas exhibited a greater rate of rise (defined as enhanced intensity divided by enhancement time) and a shorter half-clearance time (P<0.05). These findings suggest that in endometrial carcinoma, the contrast agent displays a "fast-in/fast-out/hyperenhancement" perfusion pattern. In contrast, the characteristic perfusion pattern for benign endometrial lesions is low enhancement (P<0.05). The diagnostic accuracy of CEUS in detecting myometrial invasion was 88% (22 of 25 cases). Conclusion Transvaginal CEUS is a practical and effective diagnostic imaging method for distinguishing between benign and malignant endometrial lesions. It can also be used to evaluate the depth of myometrial invasion in patients with early-stage endometrial carcinoma.

Objective To explore the application value and related factors of serum carbonic anhydraseⅢ(CAⅢ)in the clinical diagnosis of mild to moderate Alzheimer disease(AD).Methods A total of 106 elderly patients initially diagnosed with mild to moderate AD at Huashan Hospital,Fudan University from October 2020 to November 2022 were enrolled as the AD group,and 89 healthy elderly people during the same period were enrolled as the control group.The serum biochemical indicators including liver and kidney function,blood lipids,blood glucose,folic acid and homocysteine were detected in both groups.Cognitive function was assessed by Mini-mental State Examination(MMSE).Patient Health Questionnaire-9(PHQ-9)and Generalized Anxiety Disorder-7(GAD-7)were used to assess psychological status.The activities of daily living(ADL)were assessed by modified Barthel Index(BI).Serum CAⅢlevels were measured by enzyme-linked immunosorbent assay(ELISA).Correlation analysis and multivariate linear regression analysis were used to identify factors influencing serum CAⅢlevels,and receiver operating characteristic(ROC)curve analysis was performed to evaluate the diagnostic value of serum CAⅢlevels in elderly patients with mild to moderate AD.Results The MMSE score of the AD group was significantly lower than that of the control group(P＜0.001),and the PHQ-9 and GAD-7 scores were significantly higher than those of the control group(P＜0.001).The serum CAⅢlevel in the AD group was significantly lower than that in the control group(P＜0.000 1).In patients with AD,serum CAⅢlevels in patients with a disease course＞3 years,accompanied by depression or anxiety,moderate AD,and serum creatinine≤111 μmol/L were significantly lower than those in patients with a disease course≤3 years,normal emotions,mild AD,and serum creatinine＞111 μmol/L(P＜0.05).Correlation analysis and multivariate linear regression analysis showed that serum CAⅢlevels were negatively correlated with disease duration,PHQ-9 score,GAD-7 scores and severity degree,positively correlated with serum creatinine level(P＜0.05).The PHQ-9 score,severity degree,and serum creatinine level were independent related factors for serum CAⅢlevel in mild to moderate AD elderly patients(P＜0.05).ROC curve result showed that the area under the curve(AUC)of serum CAⅢin diagnosing mild to moderate AD in elderly patients was 0.946,with sensitivity and specificity of 88.79% and 96.74%,respectively.Conclusions Serum CAⅢlevels in elderly patients with mild to moderate AD are higher than those in healthy individuals.Mild AD,without depressive mood,and elevated serum creatinine levels are related factors for elevated serum CAⅢlevels in elderly AD patients.Serum CAⅢmay serve as a novel biological marker for the diagnosis of mild to moderate AD in the elderly.