[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

Objective:To explore the effectiveness, safety, and cost among urinary follicle-stimulating hormone (u-FSH), recombinant FSH (r-FSH)α, and r-FSHβ in the early follicular phase prolonged protocol for patients under 35 years old with normal ovarian function.Methods:It was a retrospective cohort study. Patients under 35 years old with normal ovarian function who underwent early follicular phase prolonged protocol for ovulation stimulation and using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization in Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2023 were recruited, including the fresh and frozen-thawed embryo transfer (FET) cycles. Patients were divided into u-FSH group, r-FSHα group, and r-FSHβ group. A total of 1 048 ovarian stimulation cycles were included, with 150 cycles, 490 cycles and 408 cycles in the three groups respectively. A total of 710 FET cycles with fresh cycle cancellation were included, with 95 cycles, 320 cycles and 295 cycles in the three groups respectively. The baseline data, pregnancy outcomes, safety, and cost were compared among the three groups. The main observation indicators were cumulative pregnancy rate and cumulative live birth rate (CLBR). A binary logistic regression model was used to control confounding factors, and to analyze the relationship between three ovulation inducing medicine and CLBR. Results:The difference in the number of oocytes retrieved among the u-FSH group, r-FSHα group, and r-FSHβ group was statistically significant [13.0 (10.0, 16.0), 14.0 (11.0, 18.0), 15.0 (11.0, 19.0), respectively, P=0.012], and the difference in the number of 2PN embryos was statistically significant [9.0 (6.0, 12.0), 10.0 (7.0, 13.0), 10.0 (7.0, 13.0), respectively, P=0.046]. There were no statistically significant differences in the number of available embryos, available embryo rate, the number of high-quality embryos, high-quality embryo rate, available blastocyst formation rate, fresh cycle clinical pregnancy rate, live birth rate in fresh cycle, cumulative pregnancy rate of frozen embryos with fresh cycle cancellation, CLBR of frozen embryos with fresh cycle cancellation, cumulative clinical pregnancy rate, CLBR, moderate to severe ovarian hyperstimulation syndrome incidence, ectopic pregnancy rate, multiple pregnancy rate and neonatal malformation rate among the three groups (all P>0.05). In terms of economy, the u-FSH group had the lowest total gonadotropin cost for each patient, while the r-FSHα group had the highest. The differences among the three groups were statistically significant [u-FSH group 4 429.08 (3 198.78, 5 044.23) yuan, r-FSHα group 6 023.72 (5 433.75, 7 529.65) yuan, r-FSHβ group 5 480.00 (4 550.90, 6 437.86) yuan, P<0.001]. Binary logistic regression analysis was conducted, using u-FSH as a control. The CLBR of the r-FSHα group and r-FSHβ group showed no statistically significant difference compared with the u-FSH group (a OR=0.95, 95% CI: 0.57-1.58, P=0.838; a OR=0.89, 95% CI: 0.54-1.48, P=0.654). Conclusion:For patients under 35 years old with normal ovarian function undergoing long protocol ovarian stimulation, the effectiveness and safety of the three ovarian-stimulating medicine are similar, but u-FSH has economic advantages.

Objective To explore the value of a clinical diagnostic model of heart failure(HF)based on disulfidptosis-related genes.Methods The differentially expressed disulfidetosis-related genes from the training set of Gene Expression Omnibus Series(GSE)57345 were obtained,and then analyzed with Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)en-richment analysis,and Metascape disease enrichment analysis.Six male C57BL/6J mice were ran-domly divided into control group(intraperitoneal injection of normal saline)and HF group(intra-peritoneal injection of isoproterenol),with 3 mice in each group.Real-time quantitative PCR was applied to detect the expression levels of key genes.Results GO enrichment analysis revealed that the differentially expressed disulfidetosis-related genes were mainly involved in platelet aggrega-tion and other aspects.KEGG showed they were significantly enriched in tight junctions,vascular smooth muscle contraction and other signaling pathways.Metascape enrichment analysis indicated that these genes were mainly related to focal glomerulosclerosis,glomerular disease,platelet dis-ease,tumor infiltration,nephrotic syndrome and other diseases.The HF group had significantly higher heart weight-to-body weight ratio,and lower ejection fraction,fractional shortening,cardiac output and stroke volume than the control group(P＜0.05,P＜0.01).The cardiac mRNA levels of BNP and MYH10 were significantly higher[1.026±0.501 vs 0.686±0.187,P=0.038;1.469(1.782,2.670)vs 0.360(0.786,1.117),P=0.000],while those of MYL6 and TLN1 was obviously lower(0.575±0.105 vs 1.000±0.202,P=0.027;0.429±0.114 vs 1.000±0.109,P=0.000)in the HF group than the control group.Conclusion Our constructed HF diagnostic model has better di-agnostic performance.

Objective To investigate the relationship between MTHFR C677T gene polymorphism and peripheral edema after intracerebral hemorrhage.Methods Two hundred and sixteen patients with hypertensive intracerebral hemorrhage were divided into edema enlargement group and edema non-enlargement group according to whether cerebral edema enlargement occurred.Clinical data of the patients were collected,and the MTHFR C677T genotype was detected.Results The level of homocysteine(Hey),vascular endothelial growth factor(VEGF)level at 72 h after admission,blood loss and incidence of venous thrombosis of lower extremity in edema enlargement group were significantly increased than those in edema non-enlargement group(P＜0.05-0.01).The frequency of TT genotype of MTHFR C677T in edema enlargement group was significantly higher than that of CT genotype,and the frequency of CT genotype was significantly higher than that of the frequency of CC genotype(all P＜0.05).There were significant differences in MTHFR C677T genotype and allele frequency between edema enlargement group and edema non-enlargement group(X2=70.668,P＜0.001;x2=84.139,P＜0.001).Multivariate Logistic regression analysis showed that VEGF level at 72 h after admission,MTHFR C677T CT genotype and TT genotype were independent risk factors for cerebral hemorrhage edema enlargement(OR=1.013,95％CI:1.007-1.019,P＜0.001;OR=5.534,95％CI:2.426-12.625,P＜0.001;OR=33.088,95％CI:9.012-121.479,P＜0.001).After adjusting for other factors,the OR of MTHFR C677CT to MTHFR C677CC was 5.53(95％CI:2.426-12.625,P＜0.05),and the OR of MTHFR C677TT to MTHFR C677CC was 33.09(95％CI:9.012-121.479,P＜0.05).The edema growth rate of TT genotype,CT genotype and CC genotype at MTHFR C677T site was significantly different(F=3.204,P=0.044).There was no significant difference in VEGF level among TT genotype,CT genotype and CC genotype of MTHFR C677T site at admission(F=0.978,P=0.379),but there was significant difference in VEGF level at 72 h after admission(F=5.819,P=0.007).Conclusion MTHFR C677T gene polymorphism is associated with secondary edema enlargement after intracerebral hemorrhage.

Objective To investigate the effects of a continuous-dose administration versus different dosage regimens of polyethylene glycol electrolyte solution(PEG)taken in two doses with a 12-hour interval on bowel cleansing efficacy,with the goal of optimizing bowel preparation protocols and improving patient tolerability.Methods 232 patients who underwent painless colonoscopy and used PEG as a bowel cleanser from June 2024 to September 2024 were selected as study subjects.Participants were divided into three groups:the control group(3.00 L PEG continuous dose),experimental group A(0.75 L+2.25 L PEG),and experimental group B(1.50 L+1.50 L PEG).All patients underwent painless colonoscopy within 4～6 h after completing PEG intake.The interval between the two doses of PEG in group A and group B was 12 h.The bowel cleansing efficacy was assessed by using the Boston bowel preparation scale(BBPS),and the rates of colon polyp detection,adverse reactions,sleep duration,and tolerability were recorded.Results There were no significant statistical differences in BBPS scores and colon polyp detection rates among the three groups(P>0.05).Experimental group B experienced the least adverse reactions,followed by experimental group A,while the control group reported the most significant adverse reactions(P<0.05).The timing of PEG administration did not have a significant impact on sleep duration among the three groups(P>0.05).Patients in experimental group B showed good tolerability to PEG and were willing to accept this bowel preparation regimen,followed by group A,while the control group exhibited the poorest tolerability,with significant statistical differences among the three groups(P<0.05).Conclusion The continuous administration and divided administration of PEG have no significant impact on the effectiveness of intestinal cleansing and the detection rate of colonic polyps.However,the divided PEG regimen with a 12 h interval results in fewer adverse reactions and better tolerance,especially the optimal regimen of taking 1.50 L PEG in two doses with a 12 h interval.

A 70-year-old male patient was treated with venetoclax 100 mg orally once daily for acute myeloid leukemia. Before treatment, laboratory tests showed serum potassium 3.61 mmol/L, serum calcium 1.88 mmol/L, inorganic phosphate 1.33 mmol/L, serum uric acid 276.3 μmol/L, aspartate aminotransferase (AST) 23 U/L, gamma-glutamyl transferase (GGT) 179 U/L, and lactate dehydrogenase (LDH) 797 U/L. Six hours later of medication, the patient experienced chest tightness, wheezing, fever with chills, and the highest body temperature was 38.3 ℃. Laboratory tests showed serum potassium 5.54 mmol/L, serum calcium 1.76 mmol/L, inorganic phosphate 3.41 mmol/L, serum uric acid 827.2 μmol/L, AST 205 U/L, GGT 157 U/L, LDH 4 789 U/L, and D-dimer 51.19 mg/L, respectively. It was considered that there was a high possibility of tumor lysis induced by venetoclax, and the drug was immediately stopped. Symptomatic treatments were given, including oxygen inhalation, electrocardiogram monitoring, fluid infusion, alkalinization of urine, and uric acid reduction. The fever of the patient was alleviated on the day of drug withdrawal, the symptoms of chest distress and asthma were improved the next day, and 3 days later, laboratory tests showed serum potassium 4.24 mmol/L, serum calcium 2.02 mmol/L, inorganic phosphate 1.76 mmol/L, serum uric acid 275.0 μmol/L, AST 37 U/L, GGT 80U/L, LDH 1 146 U/L, and D-dimer 7.97 mg/L; venetoclax treatment was resumed and the tumor lysis syndrome-related symptoms did not recur.

Objective To investigate the relationship between MTHFR C677T gene polymorphism and peripheral edema after intracerebral hemorrhage.Methods Two hundred and sixteen patients with hypertensive intracerebral hemorrhage were divided into edema enlargement group and edema non-enlargement group according to whether cerebral edema enlargement occurred.Clinical data of the patients were collected,and the MTHFR C677T genotype was detected.Results The level of homocysteine(Hey),vascular endothelial growth factor(VEGF)level at 72 h after admission,blood loss and incidence of venous thrombosis of lower extremity in edema enlargement group were significantly increased than those in edema non-enlargement group(P＜0.05-0.01).The frequency of TT genotype of MTHFR C677T in edema enlargement group was significantly higher than that of CT genotype,and the frequency of CT genotype was significantly higher than that of the frequency of CC genotype(all P＜0.05).There were significant differences in MTHFR C677T genotype and allele frequency between edema enlargement group and edema non-enlargement group(X2=70.668,P＜0.001;x2=84.139,P＜0.001).Multivariate Logistic regression analysis showed that VEGF level at 72 h after admission,MTHFR C677T CT genotype and TT genotype were independent risk factors for cerebral hemorrhage edema enlargement(OR=1.013,95％CI:1.007-1.019,P＜0.001;OR=5.534,95％CI:2.426-12.625,P＜0.001;OR=33.088,95％CI:9.012-121.479,P＜0.001).After adjusting for other factors,the OR of MTHFR C677CT to MTHFR C677CC was 5.53(95％CI:2.426-12.625,P＜0.05),and the OR of MTHFR C677TT to MTHFR C677CC was 33.09(95％CI:9.012-121.479,P＜0.05).The edema growth rate of TT genotype,CT genotype and CC genotype at MTHFR C677T site was significantly different(F=3.204,P=0.044).There was no significant difference in VEGF level among TT genotype,CT genotype and CC genotype of MTHFR C677T site at admission(F=0.978,P=0.379),but there was significant difference in VEGF level at 72 h after admission(F=5.819,P=0.007).Conclusion MTHFR C677T gene polymorphism is associated with secondary edema enlargement after intracerebral hemorrhage.