ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective To investigate the spatiotemporal distribution characteristics and potential influencing factors of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, so as to provide insights into the formulation of the echinococcosis control strategy in Qinghai Province. Methods The number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases, number of registered dogs and number of stray dogs were captured from the annual reports of echinococcosis control program in Qinghai Province from 2016 to 2022, and the detection of newly diagnosed echinococcosis cases was calculated. The number of populations, precipitation, temperature, wind speed, sunshine hours, average altitude, number of year-end cattle stock, number of year-end sheep stock, gross domestic product (GDP) per capita, and number of village health centers in each county (district) of Qinghai Province were captured from the Qinghai Provincial Statistical Yearbook, and county-level electronic maps in Qinghai Province were downloaded from the National Platform for Common Geospatial Information Services. The software ArcGIS 10.8 was used to map the distribution of newly diagnosed echinococcosis cases in Qinghai Province, and the spatial autocorrelation analysis of newly diagnosed echinococcosis cases was performed. In addition, the spacetime scan analyses of number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases and geographical coordinates in Qinghai Province were performed with the software SaTScan 10.1.2, and the spatial stratified heterogeneity of the detection of newly diagnosed echinococcosis cases was investigated with the software GeoDetector. Results A total of 6 569 426 residents were screened for echinococcosis in Qinghai Province from 2016 to 2022, and 5 924 newly diagnosed echinococcosis cases were found. The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline over years from 2016 to 2022 (χ² = 11.107, P < 0.01), with the highest detection in Guoluo Tibetan Autonomous Prefecture in 2017 (82.12/10⁵). There were spatial clusters in the detection of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2018 (Moran’s I = 0.34 to 0.65, all Z values > 1.96, all P values < 0.05), and the distribution of newly diagnosed echinococcosis cases appeared random distribution from 2019 to 2022 (Moran’s I = −0.09 to 0.04, all Z values < 1.96, all P values > 0.05). Local spatial autocorrelation analysis showed high-high clusters and low-low clusters in the detection of new diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, and space-time scan analysis showed that the first most likely cluster areas of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022 were mainly distributed in Yushu Tibetan Autonomous Prefecture and Guoluo Tibetan Autonomous Prefecture. GeoDetector-based analysis of the driving factors for the spatial stratified heterogeneity of detection of newly diagnosed echinococcosis cases in Qinghai Province showed that average altitude, number of village health centers, number of cattle and sheep stock, GDP per capita, annual average sunshine hours, and annual average temperature had a strong explanatory power for the spatial distribution of newly diagnosed echinococcosis cases, with q values of 0.630, 0.610, 0.600, 0.590, 0.588, 0.537 and 0.526, respectively. Conclusions The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline in Qinghai Province over years from 2016 to 2022, showing spatial clustering. Targeted control measures are required in cluster areas of newly diagnosed echinococcosis cases for further control of the disease.

OBJECTIVE To observe the long-term efficacy of type-Ⅰ thyroplasty under general anesthesia in the treatment of glottal insufficiency caused by unilateral vocal cord paralysis.METHODS A total of 52 patients with unilateral vocal cord paralysis who underwent type-Ⅰ thyroplasty under general anesthesia at Beijing Tongren Hospital from January 2017 to June 2023 were followed up for more than one year to analyze their efficacy.RESULTS All 52 patients underwent surgery successfully under general anesthesia,and hoarseness improved after operation.Coughing caused by drinking water was reduced or disappeared,and the vocal cords moved inward with improved glottal closure.One year after operation,there was no significant change in the position of the affected vocal cords compared to one week after surgery.The visual analog scale(VAS)scores of all patients with voice disorders decreased sequentially before surgery,one week after surgery,and one year after surgery(80.28±13.49 vs.37.78±19.15 vs.26.26±21.29,P<0.05).The preoperative and one-year postoperative voice perception assessment(GRBAS)showed statistically differences in grade(G),rough(R),breathy(B),and asthenia(A)scores(2.70±0.47 vs.1.09±0.66,2.52±0.54 vs.0.85±0.67,2.85±0.36 vs.0.67±0.65,2.74±0.44 vs.0.61±0.80,P<0.05)except for strain(S).Compared with preoperative results,one-year postoperatively showed a significant decrease in jitter and shimmer(4.61±2.61 vs.3.05±2.37,9.52±3.91 vs.7.11±2.78,P<0.05),and a significant prolongation of maximum phonation time(MPT)[(5.87±2.70)s vs.(14.50±4.30)s,P<0.05].No patients experienced perioperative adverse events.CONCLUSION Type-Ⅰ thyroplasty is an effective surgical method for treatment of vocal cord paralysis.The type-Ⅰ thyroplasty under general anesthesia is safe and effective,which not only significantly improves the symptoms of hoarseness in patients,but also has stable therapeutic effects and can maintain the results for a long time.At the same time,the patient has no pain during the procedure.

Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide.For lung adenocarcinoma,identifying specific gene mutations,fusions,and giving corresponding targeted drugs can greatly improve the survival time of the patients.Among them,anaplastic lymphoma kinase(ALK)fusion occurs in 3％-7％of non-small cell lung cancer(NSCLC).In clinical practice,a variety of detection methods can be used to determine the ALK fusion status,but false negative test results are possible.This paper retrospectively analyzed the diagnosis and treatment of a patient with lung adeno-carcinoma,judged the ALK fusion status by various detection methods.Among them,immunohistochemistry(IHC)(Ventana D5F3),RNA based next-generation sequencing(RNA-based NGS)confirmed positive echinoderm microtubule associated protein like 4(EML4)-ALK fusion,while DNA-based NGS was negative.This paper analyzed the detection methods of ALK fusion,in order to clarify which detection method is the most accurate and simple to choose in different clinical cases and guide the subsequent treatment.

Lung cancer is a major cause of cancer-related mortality worldwide. Among patients with non-small cell lung cancer (NSCLC), approximately 3%-7% harbor anaplastic lymphoma kinase (ALK) gene fusions. In recent years, multiple tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with metastatic ALK-positive NSCLC. However, disease progression due to resistance remains a challenge. This article retrospectively analyzes a case of advanced lung adenocarcinoma with the echinoderm microtubule associated protein like 4 (EML4)-ALK fusion variant 3 (V3). The patient developed resistance to Lorlatinib treatment accompanied by mesenchymal-epithelial transition factor (MET) amplification. Effective tumor control was achieved with the combined use of Crizotinib and Lorlatinib, providing a valuable reference for further exploration of treatment strategies following resistance to ALK-TKIs in clinical practice.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/genetics* ; Aminopyridines/therapeutic use* ; Crizotinib/therapeutic use* ; Drug Resistance, Neoplasm/drug effects* ; Lactams/therapeutic use* ; Lung Neoplasms/genetics* ; Oncogene Proteins, Fusion/metabolism* ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-met/metabolism* ; Pyrazoles/therapeutic use*

Objective·To identify the functional motifs of mucin 1(MUC1)involved in regulating tumor cell proliferation,migration,and stemness maintenance.Methods·Mutational characteristics of the MUC1 gene across different cancers were identified from The Cancer Genome Atlas(TCGA)database.Various MUC1 mutation sites were analyzed and localized,followed by ranking based on mutation frequency.Western blotting was used to screen high-frequency MUC1 mutants with stable protein expression.BT549 cell line with MUC1 knocked out and MCF-10A cell line were used to stably overexpress MUC1 wild-type(MUC1-WT)and mutants by using lentiviral technology.Immunofluorescence was used to detect the cellular localization of MUC1 mutants.Using MUC1-WT as a positive control and MUC1-AQA,a loss-of-function mutant,as a negative control,the biological functions of different MUC1 mutant cells were analyzed:cell proliferation ability was assessed by cell counting kit-8(CCK-8)assay and colony formation assay;cell migration ability was evaluated by wound-healing and Transwell assays;cell stemness was examined by sphere formation assay.Structural localization of MUC1 mutants was analyzed by using PyMOL software,and molecular docking analysis was performed by using a protein docking software(ZDOCK Server).Results·A total of 102 mutations located in the MUC1 coding region were identified in the TCGA database,among which five missense mutations(P418S,S251R,V359I,N271S,and N465H)exhibited higher frequencies and were located in the non-variable number of tandem repeats(non-VNTR)region.Further examination revealed that the MUC1-S251R,N271S,and V359I mutants could be stably expressed.The cellular localization assay indicated that these three mutants predominantly localized in the cytoplasm,but were also presented in the nucleus.The nuclear-to-cytoplasmic ratio showed minimal differences between MUC1-WT and the mutants.Analysis of the tumorigenic biological functions of the cells expressing different MUC1 mutants revealed that:① High expression of MUC1-WT significantly enhanced the proliferation ability of both BT549 and MCF-10A cells;the proliferation of MUC1-AQA,S251R,and N271S mutant cells was decreased compared to MUC1-WT cells,while MUC1-V359I mutant cells exhibited a similar proliferative profile to MUC1-WT cells.② The migration ability of MUC1-WT high-expressing cells was significantly enhanced,whereas MUC1-AQA cells demonstrated attenuated migration.In the BT549 cells,the migration ability of MUC1-S251R and V359I cells was similar to that of MUC1-WT cells,whereas MUC1-N271S cells showed reduced migration.In the MCF-10A cells,the migration ability of MUC1-N271S and MUC1-V359I cells was similar to that of MUC1-WT cells,whereas MUC1-S251R cells exhibited significantly decreased migration.③ Stemness was enhanced in both cell types with high MUC1-WT expression,while MUC1-AQA cells lost stemness;the cells with MUC1-N271S,V359I and MUC1-WT showed comparable maintenance of stemness,whereas MUC1-S251R cells demonstrated compromised stemness.PyMOL software analysis unveiled that MUC1-N271S and V359I were located in or around the sperm protein-enterokinase-agarin(SEA)region,specifically in the loop region and the β-sheet,respectively.The molecular docking analysis revealed that the stability of the complex formed by MUC1-WT or V359I with the extracellular domain of epidermal growth factor receptor(EGFR)surpassed that of MUC1-N271S or S251R,indicating a stability hierarchy of V359I>WT>N271S>S251R.Conclusion·MUC1 mutants exhibit diverse impacts on the biological functions of tumor cells,with their effects on proliferation correlating with the EGFR signaling pathway.MUC1-V359I is similar to MUC1-WT,indicating a negligible effect on tumor cell proliferation,migration,and stemness maintenance.Conversely,MUC1-S251 and N271 sites may be involved in the regulation of signaling pathways governing cell proliferation and migration and the MUC1-S251 site plays a critical role in maintaining cell stemness.