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BACKGROUND: Melanosis coli is characterized by brown mucosa with pigmentation. Studies have showed an increased adenoma detection rate in melanosis patients, whether it is caused by a contrast effect or an oncogenic effect is still controversial. The detection of serrated polys in melanosis patients remains unknown. AIMS: The study aimed to clarify the correlation of adenoma detection rate with melanosis coli and discuss outcomes in less-experienced endoscopists. Serrated polyp detection rate was also been investigated. METHODS: A total of 2150 patients and 39,630 controls were enrolled. A propensity score matching method was used to balance covariates between the two groups. The detection of polyps, adenomas, serrated polyps, and their features was analyzed. RESULTS: The polyp detection rate (44.65% vs 41.01%, P = 0.005) and adenoma detection rate (30.34% vs 23.92%, P < 0.001) were significantly higher, and the serrated polyp detection rate (0.93% vs 1.58%, P = 0.033) was significantly lower in melanosis coli. The percentage of low-risk adenomas (44.60% vs 39.16%, P < 0.001) and polyps with 6 to 10 mm in size (20.16% vs 16.21%, P < 0.001) were higher in melanosis coli. The detection of large serrated polyps was lower (0.11% vs 0.41%, P = 0.026) in melanosis coli. CONCLUSION: Melanosis coli correlates with an increased adenoma detection rate. The detection of large serrated polyps was lower in melanosis patients. Melanosis coli may not be considered a precancerous lesion.
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Adenoma , Doenças do Colo , Pólipos do Colo , Neoplasias Colorretais , Melanose , Humanos , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Colonoscopia , Estudos Retrospectivos , Neoplasias Colorretais/patologia , Melanose/diagnóstico , Adenoma/diagnóstico , Adenoma/patologiaRESUMO
BACKGROUND AND AIMS: Submucosal tunneling endoscopic resection (STER) has been proved to be effective and safe for esophageal submucosal tumors (SMTs) originating from the muscularis propria (MP) layer. This study was aimed to further evaluate the effectiveness, safety, and influencing factors especially the types of mucosal incision of STER in a larger population. METHODS: A total of 89 patients undergoing STER with esophageal SMTs were retrospectively enrolled in this study from May 2012 to November 2016. Clinicopathological, endoscopic, and adverse events (AEs) data were collected and analyzed. Different incision methods were compared to evaluate the optimum incision method. RESULTS: There were 27 females and 62 males with mean age of 46.5 ± 10.3 years. The medium size of the tumors was 16.0 mm (ranging 10.0-60.0 mm). Inverted T incisions were made in 29 (32.6%) patients, transverse incisions in 12 (13.5%) while longitudinal incisions in 48 (53.9%). En bloc resection was achieved in 70 (78.7%) patients. The residual rate was 1.1% (1/89), and no recurrence was noted even after piecemeal resection. The rate of AEs was 21.3% (19/89), and all of the AEs were cured without intervention or treated conservatively without the need for surgery. The en bloc resection rate was comparable among the three incision groups (P = 0.868); however, the incidence of AEs in the inverted T incision was lower than that in the longitudinal incision (P = 0.003). Fewer clips were used in the inverted T incision group than in the transverse incision group (P = 0.003). CONCLUSIONS: Although STER failed to achieve en bloc resection in 21.3% patients, it was still an effective therapy owing to low residual rate and no recurrence rate after piecemeal resection. STER was safe with no severe AEs; however, minor AEs were common. Inverted T incision seems to be the optimum entry point.
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Ressecção Endoscópica de Mucosa/métodos , Mucosa Esofágica/cirurgia , Neoplasias Esofágicas/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Surgical resection is considered the first treatment option for submucosal tumors (SMTs) originating from the muscularis propria layer while submucosal tunneling endoscopic resection (STER) is proved to be a safe and effective method for treating SMTs. This study aimed to compare video-assisted thoracoscopic enucleation (VATE) with STER for treating esophageal SMTs. METHODS: Sixty-six patients with small esophageal SMTs were prospectively randomized from July 2014 to December 2015. After exclusion of 8 patients, 58 subjects scheduled for STER or VATE were enrolled. Clinicopathological, endoscopic, and adverse events (AEs) data were collected and analyzed between STER and VATE. RESULTS: Forty-six males and 12 females with a mean age of 46.1 ± 9.4 years were randomized to the STER (n = 30) and VATE (n = 28) groups, respectively. Demographics and lesion features were similar between the two groups. Median procedure time was shorter in the STER group than the VATE group (44.5 vs. 106.5 min, P < 0.001); cost was lower in the STER group (4499.46 vs. 6137.32 USD, P = 0.010). Median decrease in hemoglobin levels post-procedure was - 1.6 g/L in the STER group and 14.7 g/L after VATE (P = 0.001). Lower postoperative pain scores were found in the STER group compared with the VATE group (2 vs. 4, P < 0.001). No recurrent or residual tumors were found in either group. En bloc resection rates, complete resection rates, hospital times, and post-procedure AEs were similar between two groups. The en bloc resection rates for SMTs < 20.0 mm were 100% in both groups while STER achieved only 71.4% en bloc resection rate for SMTs ≥ 20.0 mm. CONCLUSION: STER and VATE are comparably effective for esophageal SMTs; however, STER is superior to VATE with shorter operation time and decreased cost, and seems safer than VATE. STER is recommended for SMTs < 20.0 mm while VATE is recommended for SMTs with a transverse diameter > 35.0 mm. Clinical trail registration statement: This study is registered at http://www.chictr.org.cn/showproj.aspx?proj=4814 . The registration identification number is ChiCTR-TRC-14004759. The registration date is April 30, 2014.
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Ressecção Endoscópica de Mucosa/métodos , Mucosa Esofágica/cirurgia , Neoplasias Esofágicas/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Toracoscopia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos RetrospectivosRESUMO
In the original article, there are two errors in Table 3: 1. There were 8 patients undergoing VATE suffer from moderate fever, not 9. 2. In the fourth line of outcomes, saying "pneumothorax, moderate fever and moderate fever," "moderate fever" was repeated.
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BACKGROUND AND STUDY AIMS: At present, peroral endoscopic myotomy (POEM) has been considered as the recommended treatment for achalasia, as it causes trauma to a smaller area and has fewer short-term serious complications than other treatments. However, due to the different morphology of esophagus, not all the patients with achalasia are eligible to receive POEM surgery. And the purpose of our study was to apply Ling classification, which proser Linghu put forward in 2011, in the preoperative assessment of POEM, expecting to reduce the occurrence rate of complications during or post-POEM. PATIENTS AND METHODS: The clinical data of 341 achalasia patients were collected and classified, according to the endoscopic pictures related to the middle and the lower parts of the esophagus. The correlation between Ling classification and LESP or Eckardt score was analyzed for the efficiency estimation, and the correlation of Ling classification and incidence of complications was counted for the safety evaluation. RESULTS: Ling classification was correlated with the LESP of 95 patients and Eckardt score of 131 patients. Compared to preoperative data, post-POEM LESP and Eckardt score both decreased significantly in all types of Ling classification (p < 0.05), while no significant difference in the decrease degree of either LESP or Eckardt score was found among different types of Ling classification (p > 0.05). This means Ling classification may not directly affect the postoperative efficacy of POEM. By analyzing the correlation between Ling classification and intraoperative complications, we found that the differences of total complications, gas-related complication and mucosal injury were all significant among all types of Ling classification (p < 0.05). CONCLUSIONS: Ling classification can be applied in the preoperative assessment of the safety and efficacy of POEM, and it might provide a guideline for how to reduce the complications during POEM surgery.
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Acalasia Esofágica/classificação , Acalasia Esofágica/cirurgia , Cirurgia Endoscópica por Orifício Natural , Adolescente , Adulto , Idoso , Esofagoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Complicações Pós-Operatórias , Período Pré-Operatório , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: To date, there is still a lack of standardized management strategies for gastric low-grade dysplasia (LGD), which is a direct neoplastic precancerous lesion and requires specifically superficial destruction. Radiofrequency ablation (RFA) is expected to be an effective method for gastric LGD, but post-RFA pain may affect patients' satisfaction and compliance. The current study aimed to evaluate the value of a submucosal injection prior to RFA (SI-RFA) for postoperative pain and treatment outcomes. METHODS: Between October 2014 and July 2021, gastric LGDs without risk factors (size >2 cm, unclear boundary, and abnormal microsurface and microvascularity) undergoing regular RFA and SI-RFA were retrospectively analyzed. Postoperative pain scores, wound healing, and clinical efficacy were compared. Propensity score matching, stratified analysis, and multivariable logistic regression were performed to control the confounding variables. RESULTS: One hundred and ninety-seven gastric LGDs in 151 patients received regular RFA. Forty-nine gastric LGDs in 36 patients received SI-RFA. Thirty-six pairs of patients were selected for the assessment of postoperative pain by propensity score matching. Compared to regular RFA, SI-RFA significantly decreased the degree and duration of postoperative pain (OR, 0.32; 95% CI, 0.13-0.84; P = 0.020), improved wound healing rate (80.0% [36/45] vs . 58.9% [89/151], P = 0.012), increased the complete ablation rate (91.8% [45/49] vs . 86.3% [170/197], χ2 = 1.094, P = 0.295), but correlated with higher rates of local recurrence and progression (25.6% [10/39] vs . 13.2% [18/136], χ2 = 3.471, P = 0.062; 8.3% [3/36] vs . 0.9% [1/116], P = 0.042). The multivariable logistic regression model confirmed that submucosal injection was associated with local recurrence (OR, 2.93; 95% CI, 1.13-7.58; P = 0.027). CONCLUSIONS: Submucosal injections prior to RFA may reduce postoperative pain and scar formation while ensuring complete ablation of gastric LGD. However, local recurrence and progression should be considered seriously.
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Ablação por Radiofrequência , Neoplasias Gástricas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Ablação por Radiofrequência/métodos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Idoso , Adulto , Mucosa Gástrica/cirurgia , Dor Pós-Operatória , Resultado do Tratamento , Pontuação de PropensãoRESUMO
BACKGROUND: Increasing epidemiologic studies have shown a positive correlation between obesity and chronic diarrhea. Nevertheless, the precise etiology remains uncertain. METHODS: We performed a comprehensive proteomics analysis utilizing the data-independent acquisition (DIA) technique on jejunal tissues from patients with obesity and chronic diarrhea (OD, n = 33), obese patients (OB, n = 10), and healthy controls (n = 8). Differentially expressed proteins (DEPs) in OD vs. control and OD vs. OB comparisons were subjected to pathway enrichment and protein-protein interaction (PPI) network analysis. Machine learning algorithms were adopted on overlapping DEPs in both comparisons. The candidate protein was further validated using Western blot, immunohistochemistry (IHC), and in vitro experiments. RESULTS: We identified 189 and 228 DEPs in OD vs. control and OD vs. OB comparisons, respectively. DEPs in both comparisons were co-enriched in extracellular matrix (ECM) organization. Downregulated DEPs were associated with tight junction and ECM-receptor interaction in OD vs. control and OD vs. OB comparisons, respectively. Machine learning algorithms selected 3 proteins from 14 overlapping DEPs in both comparisons, among which collagen alpha-1(III) chain (COL3A1) was identified as a core protein in PPI networks. Western blot and IHC verified the expression of COL3A1. Moreover, the tight junction-related proteins decreased after the knockdown of COL3A1 in Caco2 intestinal cells upon PA challenge, consistent with the proteomics results. CONCLUSIONS: We generated in-depth profiling of a proteomic dataset from samples of OD patients and provided unique insights into disease pathogenesis. COL3A1 was involved in the crosstalk between obesity and intestinal homeostasis via the ECM-receptor interaction pathway.
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Colágeno Tipo III , Diarreia , Aprendizado de Máquina , Obesidade , Mapas de Interação de Proteínas , Proteômica , Humanos , Proteômica/métodos , Obesidade/metabolismo , Diarreia/metabolismo , Masculino , Feminino , Colágeno Tipo III/metabolismo , Adulto , Pessoa de Meia-Idade , Células CACO-2 , Jejuno/metabolismo , Estudos de Casos e ControlesRESUMO
Trimeresurus albolabris, also known as the white-lipped pit viper or white-lipped tree viper, is a highly venomous snake distributed across Southeast Asia and the cause of many snakebite cases. In this study, we report the first whole genome assembly of T. albolabris obtained with next-generation sequencing from a specimen collected in Mengzi, Yunnan, China. After genome sequencing and assembly, the genome of this male T. albolabris individual was 1.51 Gb in length and included 38.42% repeat-element content. Using this genome, 21,695 genes were identified, and 99.17% of genes could be annotated using gene functional databases. Our genome assembly and annotation process was validated using a phylogenetic tree, which included six species and focused on single-copy genes of nuclear genomes. This research will contribute to future studies on Trimeresurus biology and the genetic basis of snake venom.
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BACKGROUND: Obesity is associated with a significantly increased risk for chronic diarrhea, which has been proposed as Linghu's obesity-diarrhea syndrome (ODS); however, its molecular mechanisms are largely unknown. AIM: To reveal the transcriptomic changes in the jejunum involved in ODS. METHODS: In a cohort of 6 ODS patients (JOD group), 6 obese people without diarrhea (JO group), and 6 healthy controls (JC group), high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes. In another cohort of 16 ODS patients (SOD group), 16 obese people without diarrhea (SO group), and 16 healthy controls (SC group), serum diamine oxidase (DAO) and D-lactate (D-LA) concentrations were detected to assess changes in intestinal barrier function. RESULTS: The gene expression profiles of jejunal mucosa in the JO and JC groups were similar, with only 1 differentially expressed gene (DEG). The gene expression profile of the JOD group was significantly changed, with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group, 129 of which overlapped. The enrichment analysis of these DEGs showed that the biological processes such as digestion, absorption, and transport of nutrients (especially lipids) tended to be up-regulated in the JOD group, while the biological processes such as rRNA processing, mitochondrial translation, antimicrobial humoral response, DNA replication, and DNA repair tended to be down-regulated in the JOD group. Eight DEGs (CDT1, NHP2, EXOSC5, EPN3, NME1, REG3A, PLA2G2A, and PRSS2) may play a key regulatory role in the pathological process of ODS, and their expression levels were significantly decreased in ODS patients (P < 0.001). In the second cohort, compared with healthy controls, the levels of serum intestinal barrier function markers (DAO and D-LA) were significantly increased in all obese individuals (P < 0.01), but were higher in the SOD group than in the SO group (P < 0.001). CONCLUSION: Compared with healthy controls and obese individuals without diarrhea, patients with Linghu's ODS had extensive transcriptomic changes in the jejunal mucosa, likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.
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Diarreia , Perfilação da Expressão Gênica , Mucosa Intestinal , Jejuno , Obesidade , Transcriptoma , Humanos , Jejuno/metabolismo , Masculino , Projetos Piloto , Feminino , Diarreia/genética , Diarreia/etiologia , Diarreia/metabolismo , Adulto , Mucosa Intestinal/metabolismo , Obesidade/genética , Obesidade/complicações , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos , Estudos de Casos e Controles , Síndrome , Amina Oxidase (contendo Cobre)/genética , Amina Oxidase (contendo Cobre)/sangue , Amina Oxidase (contendo Cobre)/metabolismo , Biologia Computacional , Ácido Láctico/sangue , Ácido Láctico/metabolismo , Doença CrônicaRESUMO
BACKGROUND: Epidemiological data on chronic diarrhea in the Chinese population are lacking, and the association between obesity and chronic diarrhea in East Asian populations remains inconclusive. This study aimed to investigate the prevalence of chronic diarrhea and its association with obesity in a representative community-dwelling Chinese population. METHODS: This cross-sectional study was based on a multistage, randomized cluster sampling involving 3503 residents aged 20-69 years from representative urban and rural communities in Beijing. Chronic diarrhea was assessed using the Bristol Stool Form Scale (BSFS), and obesity was determined based on body mass index (BMI). Logistic regression analysis and restricted cubic splines were used to evaluate the relationship between obesity and chronic diarrhea. RESULTS: The standardized prevalence of chronic diarrhea in the study population was 12.88%. The average BMI was 24.67 kg/m 2 . Of all the participants, 35.17% (1232/3503) of participants were classified as overweight and 16.13% (565/3503) as obese. After adjustment for potential confounders, individuals with obesity had an increased risk of chronic diarrhea as compared to normal weight individuals (odds ratio = 1.58, 95% confidence interval: 1.20-2.06). A nonlinear association between BMI and the risk of chronic diarrhea was observed in community residents of males and the overall participant group ( P = 0.026 and 0.017, respectively). CONCLUSIONS: This study presents initial findings on the prevalence of chronic diarrhea among residents of Chinese communities while offering substantiated evidence regarding the significant association between obesity and chronic diarrhea. These findings offer a novel perspective on gastrointestinal health management.
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BACKGROUND AND OBJECTIVES: The clinical outcomes of gastric low-grade intraepithelial neoplasia (LGIN) exhibit significant diversity, and the current reliance on endoscopic biopsy for diagnosis poses limitations in devising appropriate treatment strategies for this disease. This study aims to establish a prognostic prediction scoring system (e-Cout system) for gastric LGIN, offering a theoretical foundation for solving this clinical challenge. METHODS: Retrospectively selecting 1013 cases meeting the inclusion and exclusion criteria from over 300,000 cases of upper gastrointestinal endoscopy performed at the Digestive Endoscopy Center of our hospital between 2000 and 2022, the cohort included 484 cases as development cohort and 529 cases for validation. Employing relevant statistical analysis, we used development cohort data to establish the e-Cout system for gastric LGIN, and further used validation cohort data to for internal validation. RESULTS: In the developmental stage, based on accordant regression coefficients, we assigned point values to six risk factors for poor prognosis: 4 points for microvessel (MV) distortion, 3 points for MV thickening, 2 points for ulcer, and 1 point each for lesion size > 2cm, disease duration > 1 year, and hyperemia and redness on the lesion surface. Patients were then categorized into four risk levels: low risk (0-1 point), medium risk (2-3), high risk (4-6), and very high risk (≥7). During the validation stage, significant differences in the three different outcomes of gastric LGIN were observed across all risk levels. The probability of reversal and progression showed a significant decrease and increase, respectively, with escalating of risk levels, and these differences were statistically significant (P< 0.001). CONCLUSIONS: The proposed e-Cout system holds promise in aiding clinicians to predict the probability and risk levels of different clinical outcomes in patients with gastric LGIN. This system is expected to provide an improved foundation and guidance for the selection of clinical strategies for this disease.
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Gradação de Tumores , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Idoso , Carcinoma in Situ/patologia , Carcinoma in Situ/diagnóstico , Estudos Retrospectivos , Fatores de Risco , AdultoRESUMO
The Brown-Spotted Pit viper (Protobothrops mucrosquamatus), also known as the Chinese habu, is a widespread and highly venomous snake distributed from Northeastern India to Eastern China. Genomics research can contribute to our understanding of venom components and natural selection in vipers. Here, we collected, sequenced and assembled the genome of a male P. mucrosquamatus individual from China. We generated a highly continuous reference genome, with a length of 1.53 Gb and 41.18% of repeat elements content. Using this genome, we identified 24,799 genes, 97.97% of which could be annotated. We verified the validity of our genome assembly and annotation process by generating a phylogenetic tree based on the nuclear genome single-copy genes of six other reptile species. The results of our research will contribute to future studies on Protobothrops biology and the genetic basis of snake venom.
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High arsenic (As) groundwater is frequently found in inland basins, but little is known about As pools in sediments and their influences on aqueous As distributions. The Hetao Basin is a typical inland basin, where groundwater As concentrations generally increase from alluvial fans to flat plain. Two sites are only 1700 m apart, but groundwater As concentrations at the depth range of 15 to 80 m are quite different, ranging from 7.0 to 31.7 µg/L at site B1 and from 5.2 to 99.8 µg/L at site B2. Sediment geochemistry and groundwater hydrochemistry at two sites were characterized. No distinct differences were observed in the bulk geochemistry of sediments. Sequential extractions of 39 sediments were conducted to determine why As was easily released to groundwater at one site and not the other. Results showed that at site B1 most of solid As was associated with amorphous Fe-(oxyhydr)oxides, whereas at site B2 the strong adsorption pool dominated. Furthermore, higher dissolved Fe2+ and lower ORP in groundwater at site B2 suggested more strongly reducing conditions compared to site B1. High concentrations of NH4 + and HCO3 - at site B2 were consistent with As release coupled to microbially induced reductive dissolution of Fe-(oxyhydr)oxides. Other processes, such as the competitive adsorption of HCO3 - , As desorption under weakly alkaline pH conditions, may also influence the partitioning of As between groundwater and sediments. This study highlights the differences in how As is associated with sediments between high and low As aquifers and the contribution of chemical characteristics to As release.
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Arsênio , Água Subterrânea , Poluentes Químicos da Água , Água Subterrânea/química , Arsênio/análise , Sedimentos Geológicos/química , Óxidos , China , Poluentes Químicos da Água/análise , Monitoramento AmbientalRESUMO
Transarterial chemoembolization (TACE) has been reported to synergize with camrelizumab in the treatment of hepatocellular carcinoma (HCC). The present study aimed to explore the potential of TACE and camrelizumab as a bridging therapy prior to surgery for patients with HCC. For this purpose, 11 patients with HCC with intermediate stage disease [classified by China Liver Cancer (CNLC) staging] who received TACE combined with camrelizumab as a bridging therapy prior to surgery were enrolled in this study. The treatment response was evaluated at 2 weeks following TACE therapy and following camrelizumab treatment. The relapse-free survival (RFS) and overall survival (OS) of the patients were calculated. The objective response and disease control rates were 72.7 and 100.0% following TACE treatment, and were 100.0 and 100.0% following camrelizumab treatment, respectively. The α-fetoprotein levels gradually decreased following TACE, camrelizumab treatment and surgical resection (all P<0.05). Of note, the CNLC stage decreased following treatment (P=0.007) and the downstaging success rate was 63.6%. In terms of survival profiles, the mean RFS (95% CI) was 14.1 (11.7-16.5) months and the 1-year RFS rate was 77.9±14.1%. Furthermore, the mean OS (95% CI) was 15.0 (13.2-16.8) months and the 1-year OS rate was 80.0±17.9%. Successful downstaging was associated with RFS (P=0.041), but not OS (P=0.221). With regard to safety, 6 (54.5%) patients experienced reactive cutaneous capillary endothelial proliferation, 5 (45.5%) patients reported pain and 4 (36.4%) patients had a fever. On the whole, the present study demonstrated that TACE plus camrelizumab may be an effective and safe strategy that has potential for use as a bridging strategy prior to surgery in patients with intermediate-stage HCC.
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Divertículo Esofágico/cirurgia , Endoscopia Gastrointestinal/métodos , Acalasia Esofágica/cirurgia , Neoplasias Esofágicas/cirurgia , Divertículo Esofágico/complicações , Ressecção Endoscópica de Mucosa/métodos , Acalasia Esofágica/complicações , Neoplasias Esofágicas/complicações , Esfíncter Esofágico Inferior/cirurgia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
On public health, the effect of economic growth in China is analyzed in this paper by using the panel threshold regression model. The empirical study from 2000 to 2017 shows that China's economic growth has a significant threshold effect on public health. After the threshold is exceeded, public health will be improved dramatically. The threshold effect is heterogeneous at the regional level. The eastern region has no threshold, and both central and western regions have a single significant threshold. However, the threshold value and threshold effect in the central and western regions are also different. The heterogeneity is caused by the different levels of regional economic development. Therefore, based on public health utility maximization, the government should make different health policies according to the characteristics of regional development.