Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Diabetic chronic wounds are characterized by difficult healing, recurrent progression, and high rates of disability and mortality, which make their clinical treatment a medical challenge urgent to be addressed. However, the complex local microenvironment conditions of chronic wounds, such as high protease activity and persistent inflammatory responses, result in low bioavailability of exogenous cytokines (e.g., chemokine CXCL12) at the wound site, limiting their clinical application. In this study, we utilized Lactobacillus plantarum WCFS1 as the chassis to develop an efficient CXCL12 delivery system based on synthetic biology. Subsequently, we evaluated the role of the engineered probiotic strain in promoting the chronic wound healing in diabetic mice. Firstly, we fused the endogenous secretion signal peptide lp_3050 (SP_{lp_3050}) of L. plantarum WCFS1 and the commonly used secretion signal peptide usp45 (SP_usp45) of lactic acid bacteria with the reporter gene gusA and inserted them into the pTRK892-P_32(pgm) plasmid by molecular cloning. Then, we prepared the engineered strains and characterized the efficacy of the two signal peptides in driving the secretion of GusA. The results showed that SP_{lp_3050} efficiently drove the secretion of GusA in L. plantarum WCFS1, increasing the activity of GusA in the culture supernatant by nearly five times compared with that of SP_{lp_3050}. Further, we fused SP_{lp_3050} and codon-optimized CXCL12 gene to construct an engineered probiotic strain Lpw-CXCL12 for CXCL12 delivery. The results demonstrated that the content of CXCL12 in the culture supernatant reached (13.40±0.20) μg/mL. Finally, we found that the engineered probiotic strain Lpw-CXCL12 accelerated chronic wound healing in a diabetic mouse model. In conclusion, these results support an engineered probiotic strain in promoting diabetic chronic wound healing, providing a new strategy and technological foundation for the management of diabetic chronic wounds in the future.
Probiotics ; Animals ; Chemokine CXCL12/biosynthesis* ; Mice ; Wound Healing ; Lactobacillus plantarum/metabolism* ; Diabetes Mellitus, Experimental/complications* ; Male

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

β-elemene has been observed to exert inhibitory effects on a multitude of tumors,primarily through multiple pathways such as the inhibition of cancer cell proliferation and the induction of apoptosis.The present study is designed to elucidate the role and underlying mechanisms of β-elemene in the thera-peutic intervention of non-small cell lung cancer(NSCLC).Both in vitro and in vivo experimental models corroborate the inhibitory potency of β-elemene on NSCLCs.Our findings indicate that β-elemene fa-cilitates the maturation of miR-127-3p by inhibiting CBX8.Functioning as an upstream regulator of MAPK4,miR-127-3p deactivates the Akt/mTOR/p70S6K pathway by targeting MAPK4,thereby inducing autophagy in NSCLCs.Additionally,β-elemene augments the packaging of miR-127-3p into exosomes via SYNCRIP.Exosomal miR-127-3p further stimulates M1 polarization of macrophages by suppressing ZC3H4.Taken together,the detailed understanding of the mechanisms through which β-elemene in-duces autophagy in NSCLCs and facilitates M1 polarization of macrophages provides compelling scientific evidence supporting its potential utility in NSCLC treatment.

Allergic diseases have continued to increase year by year causing serious physical and mental injury to patients, families and individuals. This increase has been driven by conventional environmental and nutritional changes but is also created by the continual introduction of food additives into the diet and novel interior decoration materials into the living space. The causes of allergic diseases are complex and diverse, and the medical laboratory often is not be able to identify the allergic trigger; this creates a difficult environment to identify the appropriate clinical treatment for disease prevention and control. Physicians must be able to identify these triggers to help patients avoid the underlying allergenic cause of their disease. This can only be done by actively knowing a patient′s medical history, identifying the clinical manifestations of hypersensitivity and utilizing confirmatory testing as an important clinical tool in identifying the allergic source.

Allergic diseases have continued to increase year by year causing serious physical and mental injury to patients, families and individuals. This increase has been driven by conventional environmental and nutritional changes but is also created by the continual introduction of food additives into the diet and novel interior decoration materials into the living space. The causes of allergic diseases are complex and diverse, and the medical laboratory often is not be able to identify the allergic trigger; this creates a difficult environment to identify the appropriate clinical treatment for disease prevention and control. Physicians must be able to identify these triggers to help patients avoid the underlying allergenic cause of their disease. This can only be done by actively knowing a patient′s medical history, identifying the clinical manifestations of hypersensitivity and utilizing confirmatory testing as an important clinical tool in identifying the allergic source.

Objective: To evaluate the mid- and long-term efficacy of Hybrid coronary revascularization (HCR) in the treatment of multi-vessel coronary artery disease for 5 years after operation, and to compare the operative effect with those of off-pump coronary artery bypass grafting (OPCABG) for the same period. Methods: From March 2010 to June 2013, 37 patients underwent selective staging HCR surgery (HCR group) due to multi-vessel coronary artery disease in our hospital. All patients were treated by PCI and MIDCAB subsequently. 148 patients with OPCABG completed by the same group of doctors at the same time were served as control group (OPCABG group), and the follow-up period was up to June 2018. The end point of the study was the incidence of major adverse cardiac or cerebrovascular events (MACCE) events in both groups, including cardiac death, new myocardial infarction, secondary coronary revascularization and cerebrovascular accident. Results: The clinical baseline data of the two groups were basically matched. 37 patients in HCR group were successfully operated on, and each patient was completed with LIMA-LAD bypass, 72 drug-eluting stents were implanted. 504 stents were bridged in 148 patients in OPCABG group, each patient was completed with LIMA-LAD bypass, the other target vessels were performed by sequential anastomosis with great saphenous vein as graft. The average follow-up time was 6.3 years (5.1-8.2 years). In HCR group, 33 patients(89%)completed the follow-up, of which 6 (18%) had MACCE events. In OPCABG group, 130 patients(88%)successfully completed the follow-up, of which 19 (15%) had MACCE events. There was no significant difference in MACCE-free survival rate between the two groups (HCR 81.8% vs. OPCABG 73.8%, P>0.05). Conclusion The mid- and long-term effect of HCR is similar to that of OPCABG in the treatment of multi-vessel coronary artery disease, but it has the advantages of less traumatic, faster recovery and less use of blood products. It can be widely used in patients with selective multi-vessel coronary artery disease.

Objective To figure out the status of blood glucose fluctuations in patients with type 2 diabetes mellitus(T2DM)and explore its influencing factors. Methods A total of 105 T2DM cases were subjected to multiple surveys with questionnaires pertaining to general patient information,diabetes self-management,medical responses and social support as well as rating scales for the Pittsburg Sleep Quality Index and positive and negative emotions.Furthermore,the continuous glucose monitoring system(CGMS, Medtronic) was used to examine their blood sugar dynamics. Results The outcome of dynamic blood sugar monitoring showed,the standard deviation of blood glucose(SDBG)concentration was(2.41±0.91) mmol/L,the mean amplitude of glycemic excursion(MAGE)per day was(4.01±1.86)mmol/L,the median of glycemic excursion (LAGE)was 5.3 mmol/L,the median of the M-value was 5.13 mmol/L,the median for the means of daily difference(MODD)was 1.84 mmol/L and the median for low blood glucose indexes (LBMI)was 1.08 mmol/L. According to the results derived from multiple stepwise regression analyses, which used blood sugar fluctuation parameters as the variances. The results showed that: annual family income,glycosylated hemoglobin A1c(HbA1c),and diabetes self-management were shown to account for 51.5% of total SDBG variations;HbA1c,diabetes self-management,annual family income,social support and obedience could account for 76.3% of total MAGE variations;HbA1c,negative emotions and annual family income could account for 63.8% of total LAGE variations;HbA1c,annual family income,diabetes self-management and educational status could account for 52.3% of total M-value variations; HbA1c, negative emotions, diabetes self-management, annual family income and sleep quality could account for 48.0% of total MODD variations; HbA1c, annual family income and gender could account for 20.4% of total LBMI variation. Conclusions The T2DM patients, by contrast, demonstrated greater blood sugar fluctuations. HbA1c, annual family income, diabetes self-management, sleep quality, negative emotions and obedience were the main determinants that affect such fluctuations.

BACKGROUND: Pulmonary thrombosis embolism (PTE) is one of the most severe complications of perioperative radical mastectomy. Massive PTE is often accompanied by shock and hypotension which is characterized by rapid progression and high mortality. There is no standard for the treatment of these patients, which is thoracic surgery, and it is a critical issue in the thoracic surgeons. This article summarizes and analyzes the treatment of two patients with high-risk PTE at the early stage of postoperative lung cancer in our hospital. In addition, we discusses the diagnosis and treatment strategies of these cases to provide a reference for the thoracic surgeons. METHODS: We presented two patients with high-risk PTE at the early stage after thoracic surgery for radical surgery in our hospital back in 2017. One case was treated with intravenous venous interventional thrombolysis, and the other was treated with thrombolysis alone. The treatment effect of two patients and the complications during the treatment has been recorded to detail and summarized. RESULTS: Both patients were female who aged 66 and 61 years old. The time point of pulmonary embolism was 48 h and 45 h after operation, and the time of interventional thrombolysis was 70 minutes and 50 minutes after onset respectively. After 120 minutes and 100 minutes, the drainage after interventional thrombolysis was 4,690 mL and 520 mL respectively. The hospitalization time after thrombolysis was 21 days and 14 days respectively. There was no obvious complication through a follow-up of 6 months. CONCLUSIONS Early postoperative acute massive pulmonary embolism in lung cancer should be treated with pulmonary interventional thrombolysis as soon as possible. Compared with intravenous thrombolysis, pulmonary interventional thrombolysis shows accuracy, easy controlling of dosage, fast curative effect and low bleeding risk.
Female ; Humans ; Lung Neoplasms ; surgery ; Middle Aged ; Postoperative Complications ; etiology ; therapy ; Pulmonary Embolism ; etiology ; therapy ; Retrospective Studies ; Thoracic Surgery, Video-Assisted ; adverse effects ; Thrombolytic Therapy

Objective To explore the hospitalization costs of patients with diabetic foot ulcer and analyze key influencing factors.Methods A total of 570 diabetic foot inpatients were recruited from January 2008 to March 2012 for analysis of the relationship between their hospitalization costs and clinical symptoms.The multifactor regression analysis model was used to identify main influencing factors for their hospitalization costs.Results The medical costs of such inpatients amounted to 1 9 825.6 yuan (12 476.6~32 745.9)yuan,while average hospitalization costs of the 3 401 diabetic patients admitted over the same period were but 9 757.1 yuan (6 282.1 ~ 1 5 723.7 )yuan,a difference of statistic significance.The single-factor analysis found statistical differences from the differences of hospitalization among various age,occupation,dorsal artery of foot,B ultrasound of lower extremity arteries,wagner classification,amputation,transfer,leucocyte,hemoglobin,serum albumin,serum creatinine and high density lipoprotein.Multifactor analysis found that the significant factors influencing the medical costs of inpatients were days of stay,albumin,wagner classification,dorsal artery of foot,leucocyte and age. Conclusion Hypoalbuminemia,high stage of wagner classification,weak or absent pulsation of foot dorsal artery,severe infection and aging were significant factors contributing to higher medical costs of hospitalization for patients with diabetic foot ulcer.