Research Progress of Multiple Primary Malignancies Associated With Esophageal Cancer.

With the improvement in survival of patients with tumors, and continuous advancement of diagnostic technology and treatment modalities, instances of multiple primary malignancies (MPMs) are becoming an increasingly common phenomenon. The occurrence of esophageal-relevant MPMs increases the difficulty of diagnosis and treatment, and the overall prognosis is poor. Esophageal cancer related-MPMs tend to occur in areas such as the head, neck, stomach, and lungs. "Field cancerization" is one theoretical basis for the disease, and chemoradiotherapy, environmental life factors, and gene polymorphism are etiological factors. However, the influence of new therapeutic methods on MPM is still unclear, and the relationship between gene polymorphism and MPMs related to esophageal cancer needs further elucidation. Additionally, there is a lack of unified standards for diagnosis and treatment. Therefore, this study aimed to review the causes, clinical features, and prognostic factors of MPMs related to esophageal cancer.

High glucose mediates apoptosis and osteogenesis of MSCs via downregulation of AKT-Sirt1-TWIST.

BACKGROUND: Mesenchymal stem cells have been widely used in the treatment of diabetes mellitus. However, hyperglycemia associated with DM promotes cell apoptosis and affects osteogenic differentiation of MSCs in varying degrees, leading to osteoporosis in DM patients. Therefore, in this paper, the effect of high glucose on apoptosis and osteogenesis of MSCs was investigated and underlying mechanism was further determined. METHODS AND RESULTS: Intracellular ROS levels were determined using probe DCFH-DA. MMP was detected using JC-1 staining. Cell apoptosis was detected using Annexin V-FITC/PI and Flow Cytometer. The expression of genes and protein was detected by qRT-PCR and Western blot respectively. The results showed high glucose induced MSC apoptosis but promoted its osteogenesis. Western blot analysis revealed that high glucose downregulated AKT-Sirt1-TWIST pathway. Activation of Sirt1 via SRT1720 increased TWIST expression, alleviated MSC apoptosis and promoted osteogenesis of MSCs. TWIST knockdown studies demonstrated that inhibition of TWIST intensified high glucose-induced apoptosis but promoted osteogenesis differentiation of MSCs. TWIST is likely to be a new regulator for cross talk between Sirt1 and its downstream targets. CONCLUSION: Our data demonstrates that high glucose induces MSC apoptosis and enhances osteogenesis differentiation via downregulation of AKT-Sirt1-TWIST.

[Study on Risk Assessment Model of in Vitro Diagnostic Reagent Adverse Events Based on BP Neural Network].

OBJECTIVE: To modify the monitoring process and means of adverse events in vitro diagnostic reagents,improve the quantity and quality of adverse events reported in vitro,and reduce the workload of regulatory authorities,eventually ensure the safety and effectiveness of in vitro diagnostic reagents. METHODS: The pre-filtering risk assessment system based on BP neural network was used to evaluate the adverse events of in vitro diagnostic reagents.According to the evaluation results,the administrative supervision departments took corresponding countermeasures. RESULTS: The BP neural network learned the historical data,and the risk evaluation results of the adverse events were basically consistent with the expert group. CONCLUSIONS: BP neural network can be used to evaluate the risk of adverse events and achieve risk signal aggregation of adverse events.

[Research on the Whole-process Cloud Monitoring Mode of in Vitro Diagnostic Medical Devices Adverse Events].

OBJECTIVE: To improve the monitoring mode of in vitro diagnostic medical devices adverse events. METHODS: By discussing the objective laws of the characteristics, performances and causes of in vitro diagnostic medical devices adverse events, the key points of monitoring work were clarified. RESULTS: The whole-process cloud monitoring mode for adverse events of in vitro diagnostic medical devices was constructed based on risk management, and the working procedures for the four core links i.e. collection and report, investigation, analysis and evaluation, and controlling were formulated. CONCLUSIONS: The whole-process cloud monitoring mode contributes to improve the monitoring level and efficiency of in vitro diagnostic medical devices adverse events in China, so as to strengthen risk control capability and ensure the public can use medical devices safely.

[Research on the Efficacy of Fulfillment of Medical Device Adverse Event Monitoring Entities and Safeguard Mechanism].

OBJECTIVES: To solve the problem that medical device adverse event monitoring entities perform their duties inadequately, to provide reference for perfecting the post-market surveillance system. METHODS: Through theoretical and empirical research, the paper explored the ways to improve the performance of monitoring the adverse events of medical devices. RESULTS: The survey found that the number of adverse event monitoring reports was few and the quality of report was poor. The root causes included lack of motivation of monitoring entities, the imperfect monitoring system, and the monitoring capability failure, etc. CONCLUSIONS: The methods such as strengthening the main body responsibility consciousness, establishing evaluation system and accountability system, building social work network, are beneficial to the adverse events monitoring.

[Research on Classification Monitoring Model of Medical Device Adverse Events Based on Risk Management].

OBJECTIVES: To increase the number and quality of adverse events reported in medical devices, dealing with adverse events that have occurred in time, preventing the occurrence of adverse events, and ensuring the safety of device use. METHODS: Based on risk management methods, through a comprehensive analysis of risk of adverse events, scientifically assessing the risk level and completing the classification of adverse events. Administrative supervision departments take corresponding supervision measures according to the classification results. RESULTS: Building a classification monitoring model of medical device adverse events based on risk management. CONCLUSIONS: The classification of adverse events will help the administrative supervision department to focus on the work, reduce the workload, and improve the efficiency of supervision.

Administration of Curcumin Protects Kidney Tubules Against Renal Ischemia-Reperfusion Injury (RIRI) by Modulating Nitric Oxide (NO) Signaling Pathway.

BACKGROUND/AIMS: To explore the protective effect of curcumin on renal ischemia-reperfusion injury (RIRI) in rats, and its influence on nephridial tissue's NO and cGMP levels as well as downstream signaling pathway, to elucidate the possible mechanism of curcumin on RIRI. METHODS: 36 Sprague Dawley rats (SD rats) were randomly divided into Sham group, Model group, curcumin (CUR +) Model group, 12 rats per group. They were all given RIRI model preparation by unilateral artery occlusion method. All groups' ß2-MG in urine in 24h, serum Cr and BUN were compared, and UAER were calculated. Nitric oxide synthase (NOS), cGMP-dependent protein kinase (PKG), Caspase-3 expression were all determined by western blot. Nitric oxide (NO), NOS and cGMP levels were also examined by using ELISA. All groups' nephridial histomorphology and kidney tubules score were evaluated and compared. RESULTS: ß2-MG and UAER in urine, serum Cr and BUN, in renal tissue were all elevated in Model of RIRI, indicating the success of animal model of RIRI establishment, and above index in CUR + Model group were all lower than those in Model group. Furthermore, iNOS, NO, cGMP, PKG and Caspase-3 in renal tissue were all increased in Model of RIRI, indicating the NO signaling pathway was activated, which is one of the pathogenesis of RIRI, and above index in CUR + Model group were all lower than those in Model group, suggesting that inactivation of iNOS/NO/cGMP/PKG signaling pathway is one of the reasons that explain the protective effect of curcumin in RIRI. CONCLUSION: The activation of iNOS/NO/cGMP/PKG signaling pathway and the consequent promoted apoptosis of renal tubules are significantly involved in the pathogenesis of development of RIRI, and curcumin treatment could protect renal tubules against RIRI, at least partially, by suppressing the activated iNOS/NO/cGMP/PKG signaling pathway.

Ligand-dependent corepressor acts as a novel corepressor of thyroid hormone receptor and represses hepatic lipogenesis in mice.

BACKGROUND & AIMS: Transcriptional co-regulators assist nuclear receptors to control the transcription and maintain the metabolic homeostasis. Ligand-dependent corepressor (LCOR) was reported to function as a transcriptional corepressor in vitro. We found LCOR expression decreased in fatty livers of leptin-deficient (ob/ob) mice, diet-induced obese mice, as well as patients, suggesting LCOR may play a role in lipid homeostasis. We sought to investigate the physiological role of LCOR in vivo and elucidate the underlining molecular mechanisms. METHODS: The effect of LCOR on hepatic lipid accumulation and thyroid hormone receptor (TR) mediated expression of lipogenic genes was studied in vitro and in vivo. RESULTS: Ectopic expression of LCOR via intravenous infection with LCOR adenovirus decreased the hepatic triglyceride level in wild type, ob/ob, and diet-induced obese mice. Interestingly, overexpression of LCOR repressed the thyroid hormone induced expression of lipogenic genes and non-lipogenic genes, and ameliorated hepatic steatosis in obese mice, suggesting that LCOR might regulate lipogenesis as a novel TR corepressor. Furthermore, our study revealed that LCOR could interact with TRß1 in the presence of the ligand, which resulted in competitive binding and reduced recruitment of steroid receptor coactivator-1/3 (SRC-1/3) to the promoter region of TR target genes. CONCLUSIONS: Our data suggest that LCOR is likely to suppress TRß1-mediated hepatic lipogenesis by decreasing binding and recruitment of SRCs to TRß1. Our study reveals the physiological function of hepatic LCOR in lipid metabolism and the mechanism by which LCOR regulates lipogenesis. Hepatic LCOR may be a potential target for treating hepatic steatosis.

Proximal fibular osteotomy versus high tibial osteotomy for treating knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) with varus alignment and medial space stenosis is a common degenerative disorder in the elderly. To reallocate the force bearing from the medial to the lateral compartment, the anti-varus osteotomy, including high tibial osteotomy (HTO) and proximal fibular osteotomy (PFO), corrects the mechanical lines of lower extremities using surgical methods, which alleviates the abrasion of medial cartilage and relieves pain. PFO is based on the "non-uniform settlement" theory. It is to cut small section of the proximal fibula, i.e., below the fibula head, which breaks the fibula and weakens its support for the lateral of the tibial plateau, lastly reduces the gap on the lateral side of the knee joint and offsets the knee varus deformity caused by weight bearing. We conducted this systematic review and meta-analysis to compare the clinical outcomes of PFO versus HTO intervention. METHODS: Twenty-three studies were acquired from PubMed, Embase, CNKI (China National Knowledge Infrastructure), Wanfang Database and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Mean differences (MDs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Twenty-three studies including 14 randomized controlled trials and 9 observational studies were assessed. The methodological quality of the trials ranged from low to high. The pooled results of the mean operation time (MD = - 38.75, 95% CI = - 45.66 to - 31.85, P < 0.00001), intraoperative bleeding (std. MD = - 4.12, 95% CI = - 5 to - 3.24, P < 0.00001), length of hospital stay (MD = - 3.77, 95% CI = - 4.98 to - 2.56, P < 0.00001) and postoperative complications (OR = 0.66, 95% CI = 0.37-1.18, P = 0.16) showed that the differences were statistically significant between the two interventions. The postoperative differences of visual analogue score (VAS) (MD = 0.15 95% CI = - 0.39 to 0.69, P = 0.58), hospital for Special Surgery knee score (HSS) (MD = - 2.68, 95% CI = - 6.30 to 0.94, P = 0.15), American knee society (AKS) score (MD = 0.04, 95% CI = - 0.69 to 0.77, P = 0.91), western Ontario and McMaster university of orthopedic index (WOMAC) (MD = 8.09, 95% CI = 2.06-14.13, P = 0.009) and femur-tibia angle (FTA) (MD = - 0.03, 95% CI = - 5.39 to 5.33, P = 0.99) were not statistically significant. Sensitivity analysis proved the stability of the pooled results and the publication bias was not apparent. CONCLUSIONS: PFO and HTO have the same short-term efficacy in the treatment of KOA, but PFO can reduce the operation time, intraoperative bleeding, hospital stay and postoperative complications, which has certain advantages. Clinically, for patients with many complications and poor surgical tolerance, PFO can be preferred.

Thyrotoxicosis after a massive levothyroxine ingestion: A case report.

BACKGROUND: The literature on thyrotoxicosis caused by excessive ingestion of exogenous thyroid hormone is limited, and most cases reported have involved pediatric clinical studies. CASE SUMMARY: A 21-year-old woman initially presented with palpitation and chest tightness after an overdose of levothyroxine (10 mg). The patient transiently lost consciousness and developed atrial fibrillation during hospitalization. We used propylthiouracil to decrease the peripheral conversion of T4 to T3 and inhibit the synthesis of endogenous thyroxine, propranolol to control heart rate, hydrocortisone to correct severe thyrotoxicosis, and hemoperfusion to increase levothyroxine clearance. The patient recovered and was discharged. CONCLUSION: For patients with thyrotoxicosis after taking excess levothyroxine, it is critical to monitor vital signs and initiate effective treatment.

Fluid shear stress and endothelial cells synergistically promote osteogenesis of mesenchymal stem cells via integrin ß1-FAK-ERK1/2 pathway.

Prevascularization and mechanical stimulation have been reported as effective methods for the construction of functional bone tissue. However, their combined effects on osteogenic differentiation and its mechanism remain to be explored. Here, the effects of fluid shear stress (FSS) on osteogenic differentiation of rat bone-marrow-derived mesenchymal stem cells (BMSCs) when cocultured with human umbilical vein endothelial cells (HUVECs) were investigated, and underlying signaling mechanisms were further explored. FSS stimulation for 1-4 h/day increased alkaline phosphatase (ALP) activity and calcium deposition in coculture systems and promoted the proliferation of cocultured cells. FSS stimulation for 2 h/day was selected as the optimized protocol according to osteogenesis in the coculture. In this situation, the mRNA levels of ALP, runt-related transcriptional factor 2 (Runx2) and osteocalcin (OCN), and protein levels of OCN and osteopontin (OPN) in BMSCs were upregulated. Furthermore, FSS and coculture with HUVECs synergistically increased integrin ß1 expression in BMSCs and further activated focal adhesion kinases (FAKs) and downstream extracellular signal-related kinase (ERK), leading to the enhancement of Runx2 expression. Blocking the phosphorylation of FAK abrogated FSS-induced ERK phosphorylation and inhibited osteogenesis of cocultured BMSCs. These results revealed that FSS and coculture with HUVECs synergistically promotes the osteogenesis of BMSCs, which was mediated by the integrin ß1-FAK-ERK signaling pathway.

Arthroscopic labral debridement versus labral repair for patients with femoroacetabular impingement: A meta-analysis.

OBJECTIVE: Femoroacetabular impingement (FAI) is a common cause of hip pain and even tearing of the acetabular labrum in young adults and athletes. Either arthroscopic labral debridement (LD) or labral repair (LR) technique for FAI patients is needed to choose. We conducted this systematic review and meta-analysis to compare the clinical outcomes of arthroscopic LD versus LR intervention. METHODS: The five studies were acquired from PubMed, Medline, Embase, and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Four observational studies and one prospective randomized study were assessed. The methodological quality of the trials indicated a low to moderate risk of bias. The pooled results of Non-Arthritic Hip Score (NAHS), failure rate of surgeries and complications showed that the differences were not statistically significant between the two interventions. The difference of modified Harris Hip Score (mHHS), the Visual Analogue Scale (VAS) score and satisfaction rate was statistically significant between LD and LR intervention, and LR treatment was more effective. Sensitivity analysis proved the stability of the pooled results and there were too less included articles to verify the publication bias. CONCLUSIONS: Hip arthroscopy with either LR or LD is an effective treatment for symptomatic FAI. The difference of mHHS, VAS score, and satisfaction rate was statistically significant between LD and LR intervention, and arthroscopic LR could re-create suction-seal effect, potentially reduce microinstability, which demonstrated a trend toward better clinical efficacy and comparable safety compared with LD. The arthroscopic LR technique is recommended as the optical choice for acetabular labrum tear with FAI.

ß-mercaptoethanol promotes osteogenesis of human mesenchymal stem cells via sirt1-ERK pathway.

Human umbilical cord-derived mesenchymal stem cells (hUMSCs) hold strong self-renewal capacity and low immunogenicity, which have attracted attention as potential candidates for bone repair and regeneration. However, insufficient osteogenic differentiation markedly hinders the clinical applications of hUMSCs. In the present study, the effect of ß-mercaptoethanol (BME), a small molecule antioxidant which has been identified to regulate cell proliferation and differentiation, on osteogenic differentiation of hUMSCs and underlying signaling mechanism were investigated. The results indicated that under osteogenic induction conditions, BME treatment increased the alkaline phosphatase (ALP) activity and promoted calcium mineralization in hUMSCs. The gene and protein expression of osteogenesis-related markers such as ALP, osteopontin (OPN), osteocalcin (OCN) and collagen type I (COLI) were also significantly up-regulated. Besides, BME promoted the protein expression of silent information regulator type 1 (sirt1) and stimulated the activation of extracellular signal-related kinase (ERK), contributing to increased Runx2 expression. Furthermore, blocking the expression of sirt1 attenuated BME-enhanced ERK phosphorylation and osteogenic differentiation of hUMSCs. These results indicated that BME accelerated osteogenic differentiation of hUMSCs by activating the sirt1-ERK signaling pathway, thereby providing insights into the development of MSCs-based bone regeneration strategies.