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1.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(6): 917-923, 2024 Jun 06.
Article in Chinese | MEDLINE | ID: mdl-38955742

ABSTRACT

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.


Subject(s)
Nervous System , Persistent Organic Pollutants , Prenatal Exposure Delayed Effects , Pregnancy , Humans , Female , Child , Nervous System/drug effects , Nervous System/growth & development , Maternal Exposure/adverse effects , Halogenated Diphenyl Ethers/toxicity , Hydrocarbons, Chlorinated , Child Development/drug effects , Environmental Pollutants/toxicity
2.
ESMO Open ; 9(7): 103494, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38981309

ABSTRACT

BACKGROUND: High tumor mutational burden (TMB) is one of the widely researched predictive biomarkers of immune checkpoint inhibitors and has been shown to be closely related with response to immunotherapy in multiple cancer types. However, for patients who have failed conventional therapy and are about to undergo immunotherapy, there is no consensus recommendation on the timing of tumor sampling for TMB analysis, and the effects of different therapies on TMB have not been clarified. This retrospective observational study aimed to investigate the heterogeneity of TMB and genomic mutation under the treatment pressure. PATIENTS AND METHODS: We retrospectively collected the available genomic and therapeutic information from 8051 samples across 15 tumor types (>50 samples/tumor) found in 30 published studies and investigated the distribution and heterogeneity of TMB under treatment across diverse cohorts. RESULTS: This integrated analysis has shown anticancer treatments increased TMB. Significant effects of treatment on TMB were more frequently observed in tumor types with lower treatment-naïve TMB, including breast, prostate, and pediatric cancers. For different cancer therapies, chemotherapy was prone to be correlated with an increased TMB in most cancer types. Meanwhile, the fraction of the TMB-high category of breast, prostate, and bladder cancers and glioma increased significantly after chemotherapy. Several actionable genes including ERS1 and NF1 in breast cancer, as well as some prognostic markers including TERT in bladder cancer and IDH1 in glioma, were significantly changed in post-chemotherapy tumors compared to treatment-naïve tumors. CONCLUSION: Our study reveals the heterogeneity of TMB under treatment across diverse cancer types and provides evidences that chemotherapy was associated with increases in TMB as well as the fraction of TMB-high category, suggesting that resampling tumor tissues for calculating post-chemotherapy TMB could be a better option for predicting the response to immunotherapy, especially for tumors with initially low TMB.

3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(7): 740-748, 2024 Jul 25.
Article in Chinese | MEDLINE | ID: mdl-39004991

ABSTRACT

Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m2 of Cisplatin and 30-40 mg/m2 of Mitomycin C in 3-4 L saline solution at 42-43℃. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.


Subject(s)
Cytoreduction Surgical Procedures , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms , Stomach Neoplasms , Humans , Stomach Neoplasms/therapy , Cytoreduction Surgical Procedures/methods , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Peritoneal Neoplasms/drug therapy , Hyperthermic Intraperitoneal Chemotherapy/methods , Combined Modality Therapy , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Mitomycin/administration & dosage , Mitomycin/therapeutic use , Hyperthermia, Induced/methods
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(6): 1040-1047, 2024 Jun 20.
Article in Chinese | MEDLINE | ID: mdl-38977333

ABSTRACT

OBJECTIVE: To evaluate the beneficial effects of high-flow nasal cannula (HFNC) oxygen therapy during cesarean section in pregnant women with heart disease. METHODS: We conducted a single-center, single-blinded randomized trial of HFNC oxygen therapy in pregnant women with heart disease undergoing cesarean section under neuraxial anesthesia.The participants were randomly assigned to receive either HFNC oxygen therapy with inspiratory flow of 30 L/min with 40% FIO2(n=27) or conventional oxygen therapy (COT) with oxygen flow rate of 5 L/min via a nasal cannula (n=31).The primary outcome was maternal desaturation (SpO2 < 94% lasting more than 3 min or PaO2/FIO2≤300 mmHg). RESULTS: Maternal desaturation was observed in 7.4%(2/27) of the women in HFNC group and in 32.3%(10/31) in the COT group.None of the cases required tracheal intubation during the perioperative period.The HFNC group had a significantly higher incidence of postoperative leukocytosis (P < 0.05) but without pyrexia or other inflammation-related symptoms.There were no significant differences between the two groups in the secondary maternal outcomes (need for respiratory support, maternal ICU admission, postoperative respiratory complications, and cardiovascular complications) or neonatal outcomes (P>0.05). CONCLUSION: In pregnant women with heart disease, HFNC therapy can significantly reduce the rate of maternal desaturation during the perioperative period of cesarean section without adverse effects on short-term maternal or fetal outcomes.


Subject(s)
Cesarean Section , Oxygen Inhalation Therapy , Humans , Female , Pregnancy , Oxygen Inhalation Therapy/methods , Adult , Heart Diseases/therapy , Cannula , Oxygen/administration & dosage , Single-Blind Method
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(6): 1209-1216, 2024 Jun 20.
Article in Chinese | MEDLINE | ID: mdl-38977352

ABSTRACT

OBJECTIVE: To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma (ESCC). METHODS: We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients. GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog, and TIMER online tool was used to analyze the correlations among TßR1, MMP-2, and MMP-9 in esophageal cancer. RESULTS: Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated. Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age, gender, or tumor differentiation. The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time. Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-ß signaling pathway, and the expressions of MMP-2/MMP-9 and TßR1 were positively correlated. In cultured ESCC cells, Nanog knockdown significantly decreased the expression of TßR1, p-Smad2/3, MMP-2, and MMP-9 and strongly inhibited cell migration. CONCLUSION: The high expressions of Nanog, MMP-2, and MMP-9, which are positively correlated, are closely related with invasion depth, lymph node metastasis, and prognosis of ESCC. Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-ß signaling pathway, and its high expression promotes migration of ESCC cells.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Lymphatic Metastasis , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Nanog Homeobox Protein , Neoplasm Invasiveness , Signal Transduction , Transforming Growth Factor beta , Humans , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/pathology , Nanog Homeobox Protein/metabolism , Nanog Homeobox Protein/genetics , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Esophageal Neoplasms/genetics , Transforming Growth Factor beta/metabolism , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 2/metabolism , Prognosis , Male , Female
6.
Eur Rev Med Pharmacol Sci ; 28(11): 3725-3732, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38884507

ABSTRACT

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is a widely recognized effective bariatric surgery. However, variable weight loss outcomes post-surgery remained a clinical challenge. Currently, there is no established consensus on the factors influencing weight loss failure following LSG. This study aimed to explore the association between preoperative cortisol secretion autonomy and postoperative weight loss in obese patients undergoing LSG. PATIENTS AND METHODS: A cohort of 181 patients with simple obesity (BMI ≥ 28 kg/m2) who underwent LSG and were followed up for one year was analyzed. Weight loss was measured by the percentage of excess weight loss (%EWL), and cortisol secretion autonomy was evaluated using a 1 mg dexamethasone suppression test (DST). Regression models were used to analyze the correlation between preoperative 1 mg DST results and %EWL one year after laparoscopic sleeve gastrectomy (LSG). RESULTS: Cortisol secretion autonomy was significantly lower in the %EWL ≥ 75% group and higher in the %EWL < 75% group, showing a negative correlation with %EWL (R = -0.336, p = 0.001). Logistic regression analysis indicated that high cortisol secretion autonomy was significantly correlated with %EWL < 75% after LSG. The likelihood of %EWL being < 75% was 10.47 times greater in patients with high cortisol secretion autonomy compared to those with low cortisol secretion autonomy (odds ratio 10.472, confidence interval: 1.660-66.048, p = 0.012). CONCLUSIONS: Cortisol secretion autonomy emerges as an independent predictor of weight loss outcomes in Asian patients undergoing LSG. This finding suggests the potential for cortisol secretion autonomy to inform preoperative assessments and personalized treatment strategies in bariatric surgery.


Subject(s)
Gastrectomy , Hydrocortisone , Laparoscopy , Weight Loss , Humans , Prospective Studies , Female , Hydrocortisone/metabolism , Hydrocortisone/blood , Male , Adult , Middle Aged , Bariatric Surgery , Asian People , Treatment Outcome , Cohort Studies , Obesity/surgery
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(5): 859-866, 2024 May 20.
Article in Chinese | MEDLINE | ID: mdl-38862443

ABSTRACT

OBJECTIVE: To explore differentially expressed endoplasmic reticulum stress-associated genes (ERSAGs) in aortic dissection (AD) and their correlations with immune cell infiltration to identify new therapeutic targets for AD. METHODS: Two AD mRNA expression datasets (GSE190635 and GSE98770) were downloaded from GEO database for analysis of differentially expressed genes between the aorta of AD patients and normal aorta using R software. ERSAGs dataset was downloaded from GeneCards website, and GeneMANIA database was used to analyze the protein-protein interaction network of the differentially expressed ERSAGs and the proteins interacting with these genes. Based on GSE98770 dataset we analyzed the distributions of 22 immune cells within the aortic wall of AD patients using CIBERSORT package of R software. Surgical aortic wall specimens were obtained from 10 AD patients and 10 non-AD patients for detecting AGER mRNA expression using qRTPCR, and the upstream transcriptional factors, miRNAs, and chemicals targeting AGER were analyzed using the TRRUST database and NetworkAnalyst database. RESULTS: Bioinformatic analysis suggested significant differential expression of AGER in AD, which interacted with 20 proteins involved in pattern recognition receptor signaling pathway, positive regulation of DNA-binding transcription factor activity, myeloid leukocyte migration, leukocyte migration, and regulation of the I-κB kinase/NF-κB signaling. In AD, AGER expression level was positively correlated with Treg cell abundance (r=0.59, P < 0.05). The results of qRT-PCR demonstrated significantly lower expression of AGER mRNA in AD than in non-AD patients (1.00±0.30 vs 1.76±0.68, P < 0.05). ROC curve analysis showed that at the cut-off value of 1.335, AGER had an AUC of 0.86 (95% CI: 0.67-1.00, P= 0.0073) for predicting AD. Three transcriptional factors, 3 miRNAs, and 27 chemicals were predicted in the AGER regulatory network. CONCLUSION: AGER is lowly expressed in the aorta of AD patients and may influence the occurrence of AD through Treg cells.


Subject(s)
Aortic Dissection , Endoplasmic Reticulum Stress , Humans , Aortic Dissection/genetics , Aortic Dissection/metabolism , Endoplasmic Reticulum Stress/genetics , Protein Interaction Maps/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Computational Biology , Signal Transduction , Gene Expression Profiling , Gene Regulatory Networks , Aorta/metabolism
8.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 215-224, 2024 Mar 14.
Article in Chinese | MEDLINE | ID: mdl-38716592

ABSTRACT

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.


Subject(s)
Dasatinib , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Humans , Retrospective Studies , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Protein Kinase Inhibitors/therapeutic use , Imatinib Mesylate/therapeutic use , Dasatinib/therapeutic use , China , Treatment Outcome , Male , Female , Pyrimidines/therapeutic use , Adult , Middle Aged
9.
J Endocrinol Invest ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744806

ABSTRACT

PURPOSE: We aim to detect serum DKK1 level of pediatric patients with OI and to analyze its relationship with the genotype and phenotype of OI patients. METHODS: A cohort of pediatric OI patients and age-matched healthy children were enrolled. Serum levels of DKK1 and bone turnover biomarkers were measured by enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometry. Pathogenic mutations of OI were detected by next-generation sequencing and confirmed by Sanger sequencing. RESULTS: A total of 62 OI children with mean age of 9.50 (4.86, 12.00) years and 29 healthy children were included in this study. The serum DKK1 concentration in OI children was significantly higher than that in healthy children [5.20 (4.54, 6.32) and 4.08 (3.59, 4.92) ng/mL, P < 0.001]. The serum DKK1 concentration in OI children was negatively correlated with height (r = - 0.282), height Z score (r = - 0.292), ALP concentration (r = - 0.304), lumbar BMD (r = - 0.276), BMD Z score of the lumbar spine and femoral neck (r = - 0.32; r = - 0.27) (all P < 0.05). No significant difference in serum DKK1 concentration was found between OI patients with and without vertebral compression fractures. In patients with spinal deformity (22/62), serum DKK1 concentration was positively correlated with SDI (r = 0.480, P < 0.05). No significant correlation was observed between serum DKK1 concentration and the annual incidence of peripheral fractures, genotype and types of collagen changes in OI children. CONCLUSION: The serum DKK1 level was not only significantly elevated in OI children, but also closely correlated to their skeletal phenotype, suggesting that DKK1 may become a new biomarker and a potential therapeutic target of OI.

10.
J Dent Res ; 103(6): 662-671, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38716742

ABSTRACT

Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in ENAM, which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of ENAM, c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of Enam on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)-related genes and TNFRSF10B, a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 ENAM mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an ENAM mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for ENAM-associated AI.


Subject(s)
Amelogenesis Imperfecta , Amelogenesis Imperfecta/genetics , Animals , Mice , Humans , Ameloblasts/pathology , Female , Male , Mutation , Dental Enamel Proteins/genetics , Pedigree , Apoptosis/genetics , In Situ Hybridization , Extracellular Matrix Proteins
11.
Phys Rev Lett ; 132(17): 171001, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38728703

ABSTRACT

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

12.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(5): 471-477, 2024 May 25.
Article in Chinese | MEDLINE | ID: mdl-38778687

ABSTRACT

Objective: To analyze the safety of paclitaxel-based, hyperthermic, intraperitoneal perfusion chemotherapy (HIPEC) after radical resection of locally advanced gastric cancer. Methods: This was a retrospective cohort study of clinicopathological data of 467 patients with locally advanced gastric adenocarcinoma who had been admitted to the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between July 2019 and April 2021. Among these patients, 151 had undergone radical resection combined with post-operative paclitaxel-based HIPEC (surgery+HIPEC group) and 316 radical resection alone (surgery group). The adverse perioperative events in study patients were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) published by the U.S. Department of Health and Human Services. Subgroup analysis was performed on patients in the surgery+HIPEC group according to the number of times HIPEC was administered and the incidence of adverse events was compared between subgroups using the χ2 test. Independent risk factors for paclitaxel-based HIPEC-associated adverse events were identified by applying a logistic model. Results: In the surgery+HIPEC group, there were 113 (74.8%) male and 38 (25.2%) female patients of median age 64 (55, 68) years, 18 (11.9%), 79 (52.3%), and 54 (35.8%) of whom had undergone one, two, and three paclitaxel-based HIPEC treatments, respectively, after surgery. The median maximum tumor diameter was 5.0 (3.6, 6.5) cm. In the surgery group, there were 244 (77.2%) male and 72 (22.8%) female patients of median age 63 (54, 68) and the median maximum tumor diameter was 4.0 (3.0, 5.5) cm. In the surgery+HIPEC group, 112 patients (74.2%) had 198 Grade 2 or higher adverse perioperative events, postoperative hypoalbuminemia being the commonest (85 cases, 56.3%), followed by postoperative anemia (50 cases, 33.1%). Compared with the surgery group, the incidences of postoperative hypoalbuminemia (56.3% [85/151] vs. 37.7% [119/316], χ2=14.420, P<0.001), anemia (33.1% [50/151] vs. 22.5% [71/316], χ2=6.030, P=0.014), abdominal pain [7.3% [11/151] vs. 1.6% [5/316], χ2=10.042, P=0.002) and abdominal distension (5.3% [8/151] vs. 1.3% [4/316], χ2=5.123, P=0.024) were all significantly higher in the surgery+HIPEC group. Analysis of the three HIPEC subgroups revealed significant differences in the incidences of postoperative hypoalbuminemia (13/18 vs. 67.1% [53/79] vs. 35.2% [19/54], χ2=12.955, P<0.001) and pulmonary infection (6/18 vs. 6.3% [5/79] vs. 1.9% [1/54], χ2=13.232, P<0.001) between them. Univariate analysis identified body mass index, Borrmann's type and number of HIPEC treatments as associated with perioperative adverse events in the surgery+HIPEC group (P<0.05). However, according to multifactorial logistic analysis, the above factors were not independent risk factors for perioperative adverse events in the surgery+HIPEC group (P>0.05). Conclusions: Paclitaxel-based HIPEC after radical resection significantly increases the risk of postoperative hypoalbuminemia, anemia, abdominal pain, and abdominal distension in patients who have undergone excision of locally advanced gastric cancer. However, increasing the frequency of HIPEC treatments did not significantly increase the risk of paclitaxel-based HIPEC-related adverse events. Moreover, univariate and multivariate analysis did not identify any independent risk factors for paclitaxel HIPEC-related adverse events.


Subject(s)
Hyperthermic Intraperitoneal Chemotherapy , Paclitaxel , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/therapy , Paclitaxel/administration & dosage , Male , Female , Middle Aged , Retrospective Studies , Hyperthermic Intraperitoneal Chemotherapy/methods , Aged , Combined Modality Therapy , Adenocarcinoma/therapy , Adenocarcinoma/surgery , Adult
13.
Plant Mol Biol ; 114(3): 53, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714550

ABSTRACT

Plants have a variety of regulatory mechanisms to perceive, transduce, and respond to biotic and abiotic stress. One such mechanism is the calcium-sensing CBL-CIPK system responsible for the sensing of specific stressors, such as drought or pathogens. CBLs perceive and bind Calcium (Ca2+) in response to stress and then interact with CIPKs to form an activated complex. This leads to the phosphorylation of downstream targets, including transporters and ion channels, and modulates transcription factor levels and the consequent levels of stress-associated genes. This review describes the mechanisms underlying the response of the CBL-CIPK pathway to biotic and abiotic stresses, including regulating ion transport channels, coordinating plant hormone signal transduction, and pathways related to ROS signaling. Investigation of the function of the CBL-CIPK pathway is important for understanding plant stress tolerance and provides a promising avenue for molecular breeding.


Subject(s)
Plant Proteins , Signal Transduction , Stress, Physiological , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Plants/genetics , Plants/metabolism , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Calcium/metabolism , Plant Growth Regulators/metabolism , Reactive Oxygen Species/metabolism
15.
Zhonghua Nei Ke Za Zhi ; 63(4): 378-385, 2024 Apr 01.
Article in Chinese | MEDLINE | ID: mdl-38561283

ABSTRACT

Objective: To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS). Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results: A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs. 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs. 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs. 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions: SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.


Subject(s)
Adrenal Gland Neoplasms , Cushing Syndrome , Hyperaldosteronism , Humans , Female , Cushing Syndrome/complications , Cushing Syndrome/diagnosis , Adrenal Gland Neoplasms/complications , Retrospective Studies , Hyperaldosteronism/complications , Hyperaldosteronism/diagnosis , Prognosis , Dexamethasone/therapeutic use , Aldosterone
16.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38563715

ABSTRACT

Using a stereo camera system, a new diagnostic for the safety factor of the core plasma based on the pellet ablation trail is applied on the Experimental Advanced Superconducting Tokamak (EAST). In EAST discharge No. 128 874, a shattered pellet injection system is applied to inject a shattered neon pellet into the EAST. Since the strong magnetic field in tokamaks binds the ablated pellet material, the orientation of the pellet ablation trail is the same as the local magnetic field direction. Thus, from the three-dimensional reconstruction result of the pellet ablation trail, the local safety factor q can be obtained. The motional Stark effect (MSE) diagnostic is applied to determine the safety factor q profile in this shot. The determined safety factor q results for this new diagnostic are in quantitative agreement with those from the MSE diagnostic with the mean relative difference of only 6.8%, confirming the effectiveness of this new diagnostic of the safety factor.

17.
Zhonghua Yan Ke Za Zhi ; 60(4): 343-351, 2024 Apr 11.
Article in Chinese | MEDLINE | ID: mdl-38583058

ABSTRACT

Objective: The aim of this paper is to compare the refractive correction effects of rigid gas permeable contact lenses (RGPCL) and spectacle correction in children with aphakia after congenital cataract surgery. Methods: This was a prospective non-randomized controlled trial. Children with aphakic eyes after congenital cataract surgery, who underwent vision correction in the Strabismus and Pediatric Ophthalmology Clinic of Beijing Tongren Hospital affiliated with Capital Medical University from April 2012 to November 2019, were continuously collected. Those who voluntarily chose to wear RGPCL for refractive correction were included in the experimental group. Patients with monocular disease were in trial group 1, and patients with binocular disease were in trial group 2. Patients who chose to wear frame glasses for refractive correction were included in the control group. Patients with monocular disease were in control group 1, and patients with binocular disease were in control group 2. Regional origin, medical history, and family information were collected at the first diagnosis. During the follow-up, adverse reactions occurring during the process of wearing glasses were recorded. The Teller acuity card was used for visual examination to obtain the best-corrected visual acuity and convert it into the logarithm of the minimum resolution angle. The degree of nystagmus was determined according to the amplitude and frequency of nystagmus. Treatment cost, treatment compliance, and the reasons for adopting or not adopting RGPCL were analyzed through a questionnaire completed by the parents of children with RGPCL. Results: A total of 203 children (344 eyes) who underwent congenital cataract surgery were included, including 124 males (210 eyes) and 79 females (134 eyes). The age range was 3 to 36 months. There were 28 cases in the experimental group, including 19 cases in trial group 1 and 9 cases in trial group 2. There were 175 cases in the control group, including 43 cases in control group 1 and 132 cases in control group 2. Except for 6 months of age, the visual acuity of the experimental group was better than that of the control group, and the differences were statistically significant (P<0.05). The visual acuity of children in trial group 1 was better than that of children in control group 1 at the same age. Among them, at 12 months of age [1.54 (1.27, 1.97), 1.84 (0.97, 2.12)], 18 months of age [1.27 (0.97, 1.84), 1.84 (0.97, 2.12)], 24 months of age [1.54 (1.27, 1.84), 1.84 (0.97, 2.12)], and 30 months old [0.97 (0.66, 1.27), 1.54 (0.66, 2.12)], the difference was statistically significant (P<0.001). The visual acuity of children in trial group 2 was better than that in control group 2 at the same age. Among them, at 18 months old [1.27 (0.97, 1.54), 1.27 (0.66, 2.12)], 24 months old [0.97 (0.66, 1.27), 1.27 (0.66, 2.12)], and 30 months old [1.27 (0.66, 2.12)], the difference was statistically significant (P<0.05). The remission rate of nystagmus in the experimental group was 8/9 (8 cases), the remission rate of nystagmus in the control group was 34.40% (32 cases), and the exacerbation rate was 29.03% (27 cases). The average annual cost of the experimental group was 25 125 yuan, and that of the control group was 2 511 yuan. Conclusions: RGPCL is a well-tolerated, safe, and effective treatment for infants and young children. The visual acuity and degree of nystagmus were significantly improved in children who wore RGPCL for aphakia refractive correction after congenital cataract surgery compared with spectacle correction.


Subject(s)
Aphakia , Cataract Extraction , Cataract , Contact Lenses , Nystagmus, Pathologic , Ophthalmology , Child, Preschool , Female , Humans , Infant , Male , Cataract/therapy , Cataract/congenital , Eyeglasses , Prospective Studies
18.
Br Poult Sci ; 65(3): 259-264, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38578288

ABSTRACT

1. This study focused on the relationship between MITF mRNA expression and plumage colour in quail and the effect of promoter methylation on the expression of MITF mRNA.2. The CDS region of MITF mRNA was cloned by RT-PCR, followed by DNA sequencing. The RT-qPCR method was used to analyse the expression levels of MITF mRNA in dorsal skin tissue in Korean quail and Beijing white quail. The promoter region of the MITF gene was cloned, and the CpG island was predicted by the CpGplot program. The methylation levels of the CpG island were analysed using BS-PCR technology.3. Quail MITF mRNA contains a 1,476 bp complete ORF, which encodes a 492 amino acid residue protein. The MITF protein has no signal peptide or transmembrane region. The expression of MITF mRNA in dorsal tissue of Korean quail was significantly higher than that in Beijing white quail (p < 0.01). Abundant cis-elements and a 346 bp CpG island were found in the promoter region of the MITF gene. The average methylation level of the CpG island was 22 (22%) in Korean quail, and 46 (30%) in Beijing white quail (p < 0.05).4. The hypermethylation of the MITF gene promoter region in Beijing white quail resulted in a decrease in expression level, which was related to white feather colour.


Subject(s)
Coturnix , CpG Islands , DNA Methylation , Feathers , Microphthalmia-Associated Transcription Factor , Pigmentation , Promoter Regions, Genetic , Animals , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Feathers/chemistry , Coturnix/genetics , Coturnix/metabolism , Coturnix/physiology , Pigmentation/genetics , Avian Proteins/genetics , Avian Proteins/metabolism , RNA, Messenger/metabolism , RNA, Messenger/genetics , Gene Expression , Base Sequence , Amino Acid Sequence , Male
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(2): 324-332, 2024 Feb 20.
Article in Chinese | MEDLINE | ID: mdl-38501418

ABSTRACT

OBJECTIVE: To investigate the expression of PCI Domain Containing 2 (PCID2) in gastric cancer, its effect on gastric cancer cell cycle and proliferation and the possible molecular mechanisms. METHODS: We examined PCID2 expression levels in gastric cancer and adjacent tissues from 100 patients undergoing radical gastrectomy in our hospital between January, 2012 and December, 2016, and analyzed the correlation of PCID2 expression level with cancer progression and postoperative 5-year survival rate of the patients. GO enrichment analysis was performed to identify the possible pathways that mediated the effect of PCID2 in gastric cancer progression. The effects of lentivirus-mediated PCID2 knockdown and overexpression on cell proliferation and cell cycle were analyzed in gastric cancer MGC-803 cells and in nude mice. RESULTS: PCID2 was highly expressed in gastric cancer tissues and positively correlated with peripheral blood levels of CA19-9 and CEA (P < 0.01). In gastric cancer patients, a high PCID2 expression was associated with a significantly lowered postoperative 5-year survival rate (P < 0.001) as an independent risk factor for postoperative survival (HR: 2.987, 95% CI: 1.616-5.519). The sensitivity, specificity, and area under the curve of PCID2 for predicting postoperative 5-year survival were 76.74%, 75.44%, and 0.755 (P < 0.001), respectively. GO enrichment analysis suggested that PCID2 was associated with gastric cancer cell cycle progression. PCID2 overexpression in MGC-803 cells significantly promoted cell proliferation, G1/S phase transition, expressions of cyclin D1 and CDK6, and the growth of transplanted xenograft in nude mice (P < 0.05). The expressions of p27 and p16 were significantly lowered in gastric cancer tissues, and their expression levels were negatively regulated by PCID2 expression in MGC-803 cells (P < 0.05). CONCLUSION: PCID2 is highly expressed in gastric cancer tissues in close correlation with poor prognosis of the patients. High PCID2 expression promotes gastric cancer proliferation and cell cycle progression by inhibiting the expression of p27 and p16.


Subject(s)
Percutaneous Coronary Intervention , Stomach Neoplasms , Animals , Mice , Humans , Stomach Neoplasms/metabolism , Mice, Nude , Cell Cycle , Prognosis , Cell Proliferation , Cell Line, Tumor , Nuclear Proteins
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(2): 354-362, 2024 Feb 20.
Article in Chinese | MEDLINE | ID: mdl-38501421

ABSTRACT

OBJECTIVE: To investigate the expression level of basic leucine zipper and W2 domain-containing protein 1 (BZW1) in gastric cancer, its impact on patient prognosis and the underlying mechanisms. METHODS: TIMER, UALCAN and Kaplan-Meier Plotter databases were used for analyzing BZW1 expression level gastric cancer tissues and its correlation with tumor grade and stage and the patients' prognosis. We further analyzed BZW1 expressions, disease progression, and postoperative 5-year survival in 102 patients undergoing radical surgery for gastric cancer at our hospital between January, 2014 and December, 2016. Gastric cancer MGC803 cells were examined for changes in migration, invasion, and epithelial-mesenchymal transition (EMT) following lentivirus-mediated BZW1 overexpression or knockdown. RESULTS: The protein and mRNA expressions of BZW1 in gastric cancer tissues were 3.30 and 6.54 times of those in adjacent tissues, respectively (P < 0.01). BZW1 expression in gastric cancer tissues were positively correlated with peripheral blood CEA and CA199 levels (P < 0.01). A high BZW1 expression was an independent risk factor for 5-year survival of gastric cancer patients after radical surgery (P < 0.05, HR=2.070, 95%CI: 1.021-4.196). At the cut-off value of 3.61, BZW1 expression had a sensitivity of 75.56% and a specificity of 71.93% for predicting postoperative 5-year mortality (P < 0.01). In MGC803 cells, BZW1 overexpression obviously promoted cell migration and invasion (P < 0.05), enhanced cellular expressions of N-cadherin and vimentin (P < 0.05) and inhibited the expression of E-cadherin (P < 0.05). Enrichment analysis suggested the involvement of BZW1 in the Wnt/ß-catenin signaling pathway. Western blotting confirmed that BZW1 overexpression promoted while BZW1 knockdown inhibited the expressions of Wnt3a, ß-catenin and C-myc in MGC803 cells (P < 0.05). CONCLUSION: BZW1 is highly expressed in gastric cancer tissues to affect the patient prognosis possibly by activation the Wnt/ß-catenin signaling pathway to promote EMT of gastric cancer cells.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , beta Catenin/metabolism , Wnt Signaling Pathway , Epithelial-Mesenchymal Transition , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , DNA-Binding Proteins/genetics , Cell Cycle Proteins/genetics
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