Values of D-D, CRP, ESR and Routine Blood Indicators in Perioperative Treatment of Patients with Orthopedic Trauma.

BACKGROUND: We aimed to explore the values of D-dimer (D-D), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and routine blood indicators in the perioperative treatment of patients with orthopedic trauma. METHODS: A total of 170 patients treated from January 2019 to May 2022 were enrolled and assigned into an infection group (n = 71) and a non-infection group (n = 99) according to whether they had infection in the perioperative period. The levels of D-D, CRP, ESR, and routine blood indicators were detected, and their correlations with perioperative infection were analyzed. RESULTS: The levels of D-D, CRP, ESR, procalcitonin, leukocyte and neutrophil indicators in the two groups significantly increased 3 days after surgery compared with those before surgery (p < 0.05), and they were higher in the infection group (p < 0.05). In the infection group, the D-D, CRP, and ESR levels had no significant differences between males and females or between elderly and non-elderly patients 1 and 3 days after surgery (p > 0.05). They were significantly lower in patients with good prognosis than those with poor prognosis, and significantly increased after infection in comparison with those before confirmed infection (p < 0.05). CONCLUSIONS: ESR, CRP, D-D, and routine blood indicators are of important guiding significance in the perioperative period of patients with orthopedic trauma, based on which early infection can be diagnosed.

Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet.

Over the years, pancreatic cancer has experienced a global surge in incidence and mortality rates, largely attributed to the influence of obesity and diabetes mellitus on disease initiation and progression. In this study, we investigated the pathogenesis of pancreatic cancer in mice subjected to a high-fat diet (HFD) and observed an increase in citric acid expenditure. Notably, citrate treatment demonstrates significant efficacy in promoting tumor cell apoptosis, suppressing cell proliferation, and inhibiting tumor growth in vivo. Our investigations revealed that citrate achieved these effects by releasing secreted protein acidic and rich in cysteine (SPARC) proteins, repolarizing M2 macrophages into M1 macrophages, and facilitating tumor cell apoptosis. Overall, our research highlights the critical role of citric acid as a pivotal metabolite in the intricate relationship between obesity and pancreatic cancer. Furthermore, we uncovered the significant metabolic and immune checkpoint function of SPARC in pancreatic cancer, suggesting its potential as both a biomarker and therapeutic target in treating this patient population.

Trends of gastric cancer burdens attributable to risk factors in China from 2000 to 2050.

Background: The incidence of gastric cancer (GC) decreased in past decades, which was thought largely attributable to risk factors control, yet China still accounts for 44% of global GC burdens. We aimed to estimate changing trajectories of proportions of GC burdens attributable to modifiable risk factors from 2000 to 2050 in China, to inform future targeted preventive strategies. Methods: The incidence and new cases of GC were predicted to 2050 using Bayesian age-period-cohort model based on incidence data by anatomical subsites drawn from 682 cancer registries from National Central Cancer Registry. Population attributable fractions (PAFs) were calculated based on prevalence of risk factors and relative risks with GC. Temporal trends of PAFs were described by sex and categories of risk factors using joinpoint analysis. Findings: We observed declining trends of PAFs of Helicobacter pylori (H. pylori) infection, smoking, pickled vegetable and alcohol consumption, but increasing trends of PAFs of unhealthy body mass index and diabetes for GC in China. The combined PAFs of these risk factors were estimated to decrease by 10.57% from 2000 to 2050 for GC. We estimated there will be 279,707 GC (122,796 cardia gastric cancer [CGC] and 156,911 non-cardia gastric cancer [NCGC]) cases in 2050. Out of these cases, 70.18% of GC cases could be attributable to modifiable risk factors, while H. pylori infection was predicted to be responsible for 40.7% of CGC and 62.1% of NCGC cases in 2050. Interpretation: More than half of GC remained attributable to modifiable risk factors in China. Continued effective strategies on risk factors control are needed to reduce the burden of this highly life-threatening cancer in future. Funding: Beijing Nova Program (No. Z201100006820069), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-023), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-010), Talent Incentive Program of Cancer Hospital Chinese Academy of Medical Sciences (Hope Star).

Disrupted Stiffness Ratio Alters Nuclear Mechanosensing.

The ability of endothelial cells to sense and respond to dynamic changes in blood flow is critical for vascular homeostasis and cardiovascular health. The mechanical and geometric properties of the nuclear and cytoplasmic compartments affect mechanotransduction. We hypothesized that alterations to these parameters have resulting mechanosensory consequences. Using atomic force microscopy and mathematical modeling, we assessed how the nuclear and cytoplasmic compartment stiffnesses modulate shear stress transfer to the nucleus within aging endothelial cells. Our computational studies revealed that the critical parameter controlling shear transfer is not the individual mechanics of these compartments, but the stiffness ratio between them. Replicatively aged cells had a reduced stiffness ratio, attenuating shear transfer, while the ratio was not altered in a genetic model of accelerated aging. We provide a theoretical framework suggesting that dysregulation of the shear stress response can be uniquely imparted by relative mechanical changes in subcellular compartments.

A systematic review and meta-analysis on the relative and attributable risk of Helicobacter pylori infection and cardia and non-cardia gastric cancer.

INTRODUCTION: This study aimed to update the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC). METHODS: We searched PubMed, Embase, and Cochrane Library from 1990 to December 2021 to identify prospective studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and GC. RESULTS: Including 27 studies, findings indicated a strong link between H. pylori and non-cardia gastric cancer (NCGC) in both Europe/North America (OR=5.37, 95%CI:4.39-6.57) and Asia (OR = 2.50, 95%CI:1.89-3.32), and a positive association with cardia gastric cancer (CGC) in Asia (OR = 1.74, 95%CI:1.38-2.19), but an inverse association in European/American populations (OR = 0.64, 95%CI: 0.51 to 0.79). Furthermore, the strength of association was greater in studies that detected H. pylori by immunoblotting versus ELISA, and also in studies testing for H. pylori detection further back in time prior to cancer diagnosis (Ptrend<0.05). Approximately 79% of NCGC in Asia and 87% in Europe/North America, along with 62% of CGC in Asia, could be attributable to H. pylori infection. CONCLUSIONS: The meta-analysis supports the significant attributable risk of H. pylori infection for GC and underscores the potential impact of targeting H. pylori in GC prevention programs. PROSPERO REGISTRATION: CRD42021274120.

Development of a xylose-inducible promoter and riboswitch combination system for manipulating gene expression in Fusobacterium nucleatum.

Inducible gene expression systems are important for studying bacterial gene function, yet most exhibit leakage. In this study, we engineered a leakage-free hybrid system for precise gene expression controls in Fusobacterium nucleatum by integrating the xylose-inducible expression system with the theophylline-responsive riboswitch. This innovative method enables concurrent control of target gene expression at both transcription and translation initiation levels. Using luciferase and the indole-producing enzyme tryptophanase (TnaA) as reporters, we demonstrated that the hybrid system displays virtually no observable signal in the absence of inducers. We employed this system to express FtsX, a protein related to fusobacterial cytokinesis, in an ftsX mutant strain, unveiling a dose-dependent manner in FtsX production. Without inducers, cells form long filaments, while increasing FtsX levels by increasing inducer concentrations led to a gradual reduction in cell length until normal morphology was restored. Crucially, this system facilitated essential gene investigation, identifying the signal peptidase lepB gene as vital for F. nucleatum. LepB's essentiality stems from depletion, affecting outer membrane biogenesis and cell division. This novel hybrid system holds the potential for advancing research on essential genes and accurate gene regulation in F. nucleatum. IMPORTANCE Fusobacterium nucleatum, an anaerobic bacterium prevalent in the human oral cavity, is strongly linked to periodontitis and can colonize areas beyond the oral cavity, such as the placenta and gastrointestinal tract, causing adverse pregnancy outcomes and promoting colorectal cancer growth. Given F. nucleatum's clinical significance, research is underway to develop targeted therapies to inhibit its growth or eradicate the bacterium specifically. Essential genes, crucial for bacterial survival, growth, and reproduction, are promising drug targets. A leak-free-inducible gene expression system is needed for studying these genes, enabling conditional gene knockouts and elucidating the importance of those essential genes. Our study identified lepB as the essential gene by first generating a conditional gene mutation in F. nucleatum. Combining a xylose-inducible system with a riboswitch facilitated the analysis of essential genes in F. nucleatum, paving the way for potential drug development targeting this bacterium for various clinical applications.

Incidence, process of care, and outcomes of out-of-hospital cardiac arrest in China: a prospective study of the BASIC-OHCA registry.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is an important global public health issue, but its epidemiology and outcomes in low-income and middle-income countries remain largely unknown. We aim to comprehensively describe the incidence, process of care, and outcomes of OHCA in China. METHODS: In the prospective, multicentre, population-based Baseline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA) registry study, participating sites were selected from both urban and rural areas in all seven geographical regions across China. All patients with OHCA assessed by emergency medical service (EMS) staff were consecutively enrolled from Aug 1, 2019, to Dec 31, 2020. Patients with suspected cardiac arrest assessed by bystanders whose return of spontaneous circulation was achieved without the need for defibrillation or EMS personnel cardiopulmonary resuscitation were excluded. Patients with all key variables missing were excluded, including resuscitation attempt, age, sex, witnessed status, cause, all process of care indicators, and all outcome measures. In this analysis, we included data for EMS agencies serving 25 monitoring sites (20 urban and five rural) that included the entire serving population, data for the whole of 2020, and at least 50 OHCA patients in 2020. Data were collected and reported using the Utstein template. We calculated the crude incidence of EMS-assessed OHCA in 2020. We also report data on baseline characteristics (including sex, cause, location of OHCA, and presence of shockable rhythm), process of care (including EMS response time, cardiopulmonary resuscitation, defibrillation, and advanced life support), and outcomes of non-traumatic OHCA between Aug 1, 2019, and Dec 31, 2020, including survival and survival with favourable neurological outcomes at discharge or 30 days, and at 6 and 12 months. FINDINGS: Of 115·1 million people served by the 25 participating sites, 132 262 EMS-assessed patients with OHCA were enrolled, and resuscitation was attempted for 42 054 (31·8%) patients between Aug 1, 2019, and Dec 31, 2020. The crude incidence of EMS-assessed OHCA was 95·7 per 100 000 population (95% CI 95·6-95·8) in 2020. Among 38 227 individuals with non-traumatic OHCA, 25 958 (67·9%) were male, 30 282 (79·2%) had a cardiac arrest at home, 32 523 (85·1%) had a presumed cardiac cause, and 2297 (6·0%) presented with an initial shockable rhythm. 4049 (11·5%) of 35 090 patients with an unwitnessed or bystander-witnessed OHCA received dispatcher-assisted cardiopulmonary resuscitation and 7121 (20·3%) received bystander cardiopulmonary resuscitation; only 14 (<0·1%) patients were assessed by bystanders with an automated external defibrillator. The median EMS response time was 12 min (IQR 9-16). At hospital discharge or 30 days, 441 (1·2%) of 38 227 survived, 304 (0·8%) survived up to 6 months, and 269 (0·7%) up to 12 months. At hospital discharge or 30 days, 309 (0·8%) survived with favourable neurological outcomes, 257 (0·7%) had favourable neurological outcomes at 6 months, and 236 (0·6%) at 12 months. INTERPRETATION: Our findings revealed a high burden of EMS-assessed OHCA with a low proportion of resuscitation attempts. The suboptimal implementation of chain of survival and unsatisfactory prognosis call for national efforts to improve the care and outcomes of patients with OHCA in China. FUNDING: The National Science & Technology Fundamental Resources Investigation Program of China, the State Key Program of the National Natural Science Foundation of China, Taishan Pandeng Scholar Program of Shandong Province, the Key Research & Development Program of Shandong Province, the Interdisciplinary Young Researcher Groups Program of Shandong University, the Clinical Research Center of Shandong University, the ECCM Program of Clinical Research Center of Shandong University, and the Natural Science Foundation of Shandong Province.

Development of a Xylose-Inducible Promoter and Riboswitch Combination System for Manipulating Gene Expression in Fusobacterium nucleatum.

Inducible gene expression systems are important for studying bacterial gene function, yet most exhibit leakage. In this study, we engineered a leakage-free hybrid system for precise gene expression controls in Fusobacterium nucleatum by integrating the xylose-inducible expression system with the theophylline-responsive riboswitch. This innovative method enables concurrent control of target gene expression at both transcription and translation initiation levels. Using luciferase and the indole-producing enzyme tryptophanase (TnaA) as reporters, we demonstrated that the hybrid system displays virtually no observable signal in the absence of inducers. We employed this system to express FtsX, a protein related to fusobacterial cytokinesis, in an ftsX mutant strain, unveiling a dose-dependent manner in FtsX production. Without inducers, cells form long filaments, while increasing FtsX levels by increasing inducers concentrations led to a gradual reduction in cell length until normal morphology was restored. Crucially, this system facilitated essential gene investigation, identifying the signal peptidase lepB gene as vital for F. nucleatum . LepB's essentiality stems from depletion, affecting outer membrane biogenesis and cell division. This novel hybrid system holds the potential for advancing research on essential genes and accurate gene regulation in F. nucleatum .

A near-infrared probe for detecting and interposing amyloid beta oligomerization in early Alzheimer's disease.

BACKGROUND: The misfolding and deposition of amyloid beta (Aß) in human brain is the main hallmark of Alzheimer's disease (AD) pathology. One of the drivers of Alzheimer´s pathogenesis is the production of soluble oligomeric Aß, which could potentially serve as a biomarker of AD. METHODS: Given that the diphenylalanine (FF) at the C-terminus of Aß fragments plays a key role in inducing the AD pathology, based on the hydrophobic structure of FF, we synthesized a near-infrared BF2-dipyrrolmethane fluorescent imaging probe (NB) to detect both soluble and insoluble Aß. RESULTS: We found that NB not only binds Aß, particularly oligomeric Aß, but also interposes self-assembly of Aß through π-π interaction between NB and FF. CONCLUSION: This work holds great promise in the early detection of AD and may also provide an innovative approach to decelerate and even halt AD onset and progression.

Pre-anesthetic use of butorphanol for the prevention of emergence agitation in thoracic surgery: A multicenter, randomized controlled trial.

Background: Emergence agitation (EA) is common in patients after general anesthesia (GA) and is associated with poor outcomes. Patients with thoracic surgery have a higher incidence of EA compared with other surgery. This study aimed to investigate the impact of pre-anesthetic butorphanol infusion on the incidence of EA in patients undergoing thoracic surgery with GA. Materials and methods: This prospective randomized controlled trial (RCT) was conducted in 20 tertiary hospitals in China. A total of 668 patients undergoing elective video-assisted thoracoscopic lobectomy/segmentectomy for lung cancer were assessed for eligibility, and 620 patients were enrolled. In total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. Patients in the intervention group received butorphanol 0.02 mg/kg 15 min before induction of anesthesia. Patients in the control group received volume-matched normal saline in the same schedule. The primary outcome was the incidence of EA after 5 min of extubation, and EA was evaluated using the Riker Sedation-Agitation Scale (RSAS). The incidence of EA was determined by the chi-square test, with a significance of P < 0.05. Results: In total, 296 patients who received butorphanol and 306 control patients were included in the intention-to-treat analysis. The incidence of EA 5 min after extubation was lower with butorphanol treatment: 9.8% (29 of 296) vs. 24.5% (75 of 306) in the control group (P = 0.0001). Patients who received butorphanol had a lower incidence of drug-related complications (including injecting propofol pain and coughing with sufentanil): 112 of 296 vs. 199 of 306 in the control group (P = 0.001) and 3 of 296 vs. 35 of 306 in the control group (P = 0.0001). Conclusion: The pre-anesthetic administration of butorphanol reduced the incidence of EA after thoracic surgery under GA. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=42684], identifier [ChiCTR1900025705].

Association between CDH1 methylation and esophageal cancer risk: a meta-analysis and bioinformatics study.

OBJECTIVE: The aim is to evaluate the association of CDH1 methylation with esophageal cancer (EC) risk. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify relevant articles. Pooled odds ratios (ORs) with 95% confidence interval (CI) were estimated using the fixed- or random-effects models. The pooled sensitivity and specificity were calculated to assess the diagnostic value of CDH1 methylation for EC. The results of the meta-analysis were validated using The Cancer Genome Atlas and Gene Expression Omnibus databases. RESULTS: Thirteen studies consisting of 1,633 samples were included. A high CDH1 methylation was significantly associated with an increased risk of EC (OR = 10.40, 95% CI = 6.29-17.18). Furthermore, CDH1 methylation status was related to tumor status, lymph node status, and metastasis. For the diagnosis of EC, the pooled sensitivity and specificity of CDH1 methylation were 0.57 (95% CI = 0.39-0.74) and 0.89 (95% CI = 0.81-0.94), respectively. Bioinformatics analysis showed that CDH1 methylation occurred more frequently in EC tissues than in normal controls, in good agreement with the results of the meta-analysis. CONCLUSION: A significant association was found between CDH1 methylation and EC risk. We therefore suggest that CDH1 methylation can serve as a promising diagnostic marker for EC.

Pathology confirmation of the efficacy and safety of microwave ablation in papillary thyroid carcinoma.

Background: The incidence of papillary thyroid carcinoma (PTC) has rapidly increased in recent years. Microwave ablation (MWA) was proposed as an alternative treatment for PTC. This study aimed to investigate the efficacy and safety of MWA by exploring the postoperative pathology results of post-ablation lesions in patients with PTC. Methods: This study retrospectively analyzed data from 12 patients who underwent thyroid surgery after MWA treatment for primary PTC between January 2015 and November 2021 in six hospitals. Results: The average age of the 12 patients (8 female) was 45.3 ± 9.7 years. There was one patient with PTC (size > 1 cm) and 11 patients with micro-PTC (size ≤ 1 cm), of which eight patients had unifocal micro-PTC and three patients had multifocal micro-PTC. A total of 17 tumor foci with mean size of 6.2 ± 2.6 mm were treated by MWA. The median interval time between MWA and surgery was 6.6 months (range: 0.4-21.9 months). Intraoperatively, adherence to the anterior cervical muscle group was observed in three cases (3/12). Upon postoperative pathologic examination, all the post-ablation lesions of the eight unifocal micro-PTC and two multifocal micro-PTC showed no residual carcinomas. Outside the ablation zone, PTCs were detected in three cases, including two of the eight patients with unifocal micro-PTC and one of the three patients with multifocal micro-PTC. Cervical lymph node metastases were detected in seven patients (7/12). Conclusion: MWA was feasible for the treatment of primary unifocal low-risk micro-PTC (T1aN0M0) with good efficacy and safety. However, the use of MWA for treating PTC (size > 1 cm) and multifocal micro-PTC remains controversial.

Correlation Analysis of Magnetic Resonance Imaging Characteristics and Prognosis of Invasive Pituitary Adenomas in Neurosurgery Hospitals.

The incidence of pituitary adenoma is second only to glioma and meningioma, and its incidence ranks third among intracranial tumors. Most pituitary adenomas are benign and noninvasive tumors, but invasive pituitary adenomas pose a great threat to human health. In order to explore the risk factors that affect the clinical aggressive behavior of patients with pituitary adenoma, analyze the correlation between different classification methods and clinical aggressive behavior, and lay the foundation for early judgment and individualized treatment of clinical aggressive behavior of patients with pituitary adenoma. We conducted statistical research on patients who were treated for pituitary adenomas in the city's Yangzhou Hongquan Hospital. The results of the study showed that six patients in this study showed aggressiveness in the clinical symptomatic outcome, six patients showed aggressiveness in the serological outcome, and seven patients showed aggressiveness in imaging. In the multimodal classification, the clinical aggressiveness of pituitary adenomas in the invasion + atypical group was significantly higher than that in other groups, and the difference was statistically significant (P < 0.05). The correlation analysis of magnetic resonance imaging features and prognosis of invasive pituitary adenomas were verified to be feasible for the treatment of patients.

Papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis and breast cancer: A case report.

BACKGROUND: The recognized pattern of cervical lymph node metastasis (CLNM) of papillary thyroid carcinoma involves a stepwise route. Contralateral lymph node skip metastasis is very rare. In addition, the patient in our case report also suffered from a breast carcinoma accompanied by left supraclavicular lymphadenopathy, which made it difficult to distinguish the origin of the CLNM. Based on this case, we recommended that more detailed physical and imaging examinations are needed for patients with uncommon cervical lymphatic metastasis of primary cancer. CASE SUMMARY: A 53-year-old women was admitted to the hospital for a neck mass in the left cervical region that had existed for 2 mo. The neck mass was suspected to be an enlarged lateral LN originating from papillary thyroid microcarcinoma of the contralateral thyroid lobe, according to ultrasound and ultrasound-guided fine needle aspiration biopsy. The patient underwent total thyroidectomy and radical cervical LN dissection. Postoperative pathology confirmed the diagnosis of papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis. Unfortunately, a breast cancer was discovered 4 mo later, which was accompanied by ipsilateral supraclavicular LN metastasis. She accepted neoadjuvant chemotherapy and subsequent left modified radical mastectomy for treatment. The patient is currently receiving postoperative radiotherapy, and no local recurrence was observed in the 6-mo follow-up after surgery. CONCLUSION: We present a rare case of papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis and breast cancer with supraclavicular lymphatic metastasis.

Microbial Diversity and Composition in Six Different Gastrointestinal Sites among Participants Undergoing Upper Gastrointestinal Endoscopy in Henan, China.

The objective of this study was to describe and compare the dynamic microbiota characteristics in the gastrointestinal (GI) tract in Chinese participants via high-throughput sequencing techniques. The study collected saliva, esophageal swab, cardia biopsy, noncardia biopsy, gastric juice, and fecal specimens from 40 participants who underwent upper GI tract cancer screening in Linzhou (Henan, China) in August 2019. The V4 region of 16S rRNA genes was amplified and sequenced using the Illumina MiniSeq platform. The observed amplicon sequence variants (ASVs) gradually decreased from saliva to esophageal swab, cardia biopsy, noncardia biopsy, and gastric juice specimens and then increased from gastric juice to fecal specimens (P < 0.05). Each GI site had its own microbial characteristics that overlapped those of adjacent sites. Characteristic genera for each site were as follows: Neisseria and Prevotella in saliva, Streptococcus and Haemophilus in the esophagus, Helicobacter in the noncardia, Pseudomonas in gastric juice, Faecalibacterium, Roseburia, and Blautia in feces, and Weissella in the cardia. Helicobacter pylori-positive participants had decreased observed ASVs (cardia, P < 0.01; noncardia, P < 0.001) and Shannon index values (cardia, P < 0.001; noncardia, P < 0.001) compared with H. pylori-negative participants both in cardia and noncardia specimens. H. pylori infection played a more important role in the microbial composition of noncardia than of cardia specimens. In gastric juice, the gastric pH and H. pylori infection had similar additive effects on the microbial diversity and composition. These results show that each GI site has its own microbial characteristics that overlap those of adjacent sites and that differences and commonalities between and within microbial compositions coexist, providing essential foundations for the continuing exploration of disease-associated microbiota. IMPORTANCE Upper gastrointestinal (UGI) tract cancer is one of the most common cancers worldwide, while limited attention has been paid to the UGI microbiota. Microbial biomarkers, such as Fusobacteria nucleatum and Helicobacter pylori, bring new ideas for early detection of UGI tract cancer, which may be a highly feasible method to reduce its disease burden. This study revealed that each gastrointestinal site had its own microbial characteristics that overlapped those of adjacent sites. There were significant differences between the microbial compositions of the UGI sites and feces. Helicobacter pylori played a more significant role in the microbial composition of the noncardia stomach than in that of the cardia. Gastric pH and Helicobacter pylori had similar additive effects on the microbial diversity of gastric juice. These findings played a key role in delineating the microbiology spectrum of the gastrointestinal tract and provided baseline information for future microbial exploration covering etiology, primary screening, treatment, outcome, and health care products.

Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study.

BACKGROUND: Early diagnosis and treatment of esophageal squamous cell dysplasia (ESCdys) and esophageal squamous cell carcinoma (ESCC) could significantly reduce the incidence and mortality of ESCC. This pilot study aimed to investigate whether P16/CDKN2A methylation could serve as a cytologic biomarker for early detection of ESCdys and ESCC. METHODS: Paired esophageal biopsy and cytology specimens (exfoliated cells) were obtained from subjects at different stages of ESCC development. The methylation status of P16 gene in these two specimen types was determined using a 115-bp MethyLight assay. Categorical data were compared by the Chi-square test. Logistic regression was performed to assess adjusted odds ratios of P16 methylation associated with ESCC and ESCdys. Prediction models for identifying individuals at risk of ESCC and high-grade ESCdys (high-grade intraepithelial neoplasia, HGIN) were developed by multivariable logistic regression. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Internal validation of the prediction models was performed using the 1000-bootstrap resample. RESULTS: A total of 105 subjects with diagnoses ranging from normal mucosa through ESCC were included in this study. An increase in P16 methylation frequency was observed with increasing severity of esophageal lesions (p for trend <0.001). In the adjusted logistic regression models, P16 methylation in cytology specimens was positively associated with ESCC and ESCdys risk, whereas P16 methylation in biopsy specimens was only associated with a higher risk of developing ESCC. The predictive capacity of base model I (AUC, 0.816) for ESCC and HGIN was significantly increased by adding P16 methylation in cytology specimens (model III; AUC, 0.882; p = 0.043), but not P16 methylation in biopsy specimens (model II; AUC, 0.850; p = 0.225). Bootstrap validation showed optimism-corrected AUC of 0.789 for model I, 0.822 for model II, and 0.854 for model III. CONCLUSION: P16 methylation as a cytologic marker was associated with the ESCC development and has the potential for application in minimally invasive ESCC screening.

Salivary biomarkers-assisted ultrasound-based differentiation of malignant and benign thyroid nodules.

BACKGROUND: The incidence of papillary thyroid cancer (PTC) is increasing annually. ultrasonography (US) is the current primary method for evaluating thyroid nodules; however, there have been persisting challenges in diagnosing borderline malignancies. This paper aimed to establish the differential diagnostic value of salivary biomarkers for thyroid nodules geared towards improving the efficacy of US. METHODS: We recruited a total of 44 PTC patients and 42 benign thyroid tumor (BTT) patients to this study. The distribution of tumor markers and thyroid hormones in saliva and serum were compared between groups; then, uni-/multi-variate logistic analyses were used to determine the risk factors of PTC. Further, we estimated the differential diagnostic value of biomarkers in thyroid nodules, especially in borderline scenarios. Finally, a multi-index diagnostic model was constructed constituting biomarkers and US. RESULTS: The distributions of serum thyroglobulin (TG), salivary triiodothyronine (T3), free-triiodothyronine (FT3), and free-thyroxine (FT4) were significantly different in BTT and PTC (P<0.05); salivary FT3 was identified as an independent risk factor for PTC. By analyzing the diagnostic accuracy of various Thyroid Imaging Reporting and Data System (TI-RADS) categories, category 4A was shown to have the lowest diagnostic accuracy (48.39%) with the largest proportion (31 people, 36.05%). In 4A patients, the K-nearest neighbor (KNN) algorithm attained the highest sensitivity of 87.50% and specificity of 100.00% among the machine learning-based multi-biomarkers models. Eventually, by combing the US with the KNN-based biomarkers model, the sensitivity and specificity reached 90.91% and 83.33%, respectively. CONCLUSIONS: Salivary biomarkers exhibit good potential in the differential diagnosis of borderline thyroid nodules and they significantly improve the prediction accuracy of the US. Additionally, we found that salivary FT3 is an independent risk factor for PTC and may be used as a key marker for PTC diagnosis.

Hyaluronic Acid Modified Curcumin-Loaded Chitosan Nanoparticles Inhibit Chondrocyte Apoptosis to Attenuate Osteoarthritis via Upregulation of Activator Protein 1 and RUNX Family Transcription Factor 2.

Hyaluronic acid (HA) and curcumin (CUR) have been previously utilized for osteoarthritis (OA) treatment. CUR-loaded chitosan nanoparticles (CUR@CS NPs) and HA CUR@CS NPs were synthesized in our research to ascertain the synergistic impacts of HA and CUR-loaded NPs on OA treatment. CUR@CS NPs and HA CUR@CS NPs were synthesized with evaluation of their particle size, potential, PDI, encapsulation efficiency, drug loading and surface coating as well as HA binding rate. The in vitro CUR release curve and stability of HA-CUR@CS NPs were measured. Chondrocytes were isolated from the cartilages of OA patients, followed by cell uptake assay. The chondrocyte viability and apoptosis were determined. Subsequently, the knee OA model was established, followed by H&E, Safranin O/Fast green staining and micro-CT. HA CUR@CS NPs improved CUR stability and bioavailability. CUR@CS NPs and HA-CUR@CS NPs were successfully characterized and could further be internalized by chondrocytes. CUR@CS NPs promoted tBHP-induced chondrocyte viability and inhibited chondrocyte apoptosis. HA-CUR@CS NPs upregulated the AP-1 and RUNX2 transcription levels to activate Hedgehog pathway, which subsequently blocked the Notch pathway. Mechanically, HA-CUR@CS NPs sustained release and long-lasting effect and long-term retention in the joint cavity and downregulated the expression of several pro-inflammatory cytokines in vivo. HA-CUR@CS NPs exhibited superior effects in the preceding experiments than CUR@CS NPs. Altogether, HA-CUR@CS NPs may restrict inflammation and chondrocyte apoptosis in OA through upregulation of AP-1 and RUNX2.

Robustness of Propofol and Sevoflurane on the Perioperative Immune Function of Patients Undergoing Laparoscopic Radical Nephrectomy.

Objective. This study aimed to evaluate the robustness of propofol combined with sevoflurane in patients undergoing laparoscopic radical nephrectomy and its influence on immune function during perioperative period. A total of 140 patients who underwent laparoscopic nephrectomy in the Department of Oncology of our hospital from January 2018 to January 2020 were divided into the control group and the study group by the random number table method, with 70 cases in each group, who were given sevoflurane anesthesia and sevoflurane combined with propofol anesthesia, respectively. The anesthesia effect and perioperative immune function of the two groups of patients were compared. No remarkable difference was observed in the extubation time, breathing recovery time, and awakening time between the two groups; the extubation coughing score and postextubation restlessness score of the study group were significantly lower than those of the control group; the postoperative renal function indexes of the two groups of patients were not considerably different; after treatment, the CD3+ (%), CD4+ (%), and CD4+/CD8+ of the two groups of patients decreased significantly, with a higher level in the study group. For patients undergoing laparoscopic radical nephrectomy, the combination of propofol and sevoflurane yields a promising outcome in enhancing the anesthesia results and improving the perioperative immune function.