Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Based on the investigative research of the construction, implementation, and assessment of ideological and political education in the Cardiology curriculum at Tongji University, three main problems were concluded: the teaching methods were not suitable for the current needs of ideological and political construction in the curriculum; the professional knowledge teaching and ideological and political education were disconnected; and the quality of teaching evaluation was not high. The teaching team conducted detailed research and exploration through reforming the teaching mode, building an ideological and political material library and innovating the integration of ideological and political education with the curriculum, and innovating the evaluation system for the professional learning and ideological and political education of the curriculum, and designed an innovative method to implement curriculum ideology and politics based on material library refining combined with investigation feedback. Teaching practice verified that the method could effectively solve the three problems. The effectiveness monitoring after class demonstrated that the new method achieved the expected results, and the ideological and political construction of the Cardiology curriculum had significant improvements, proving that the method is practical and worth being promoted.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Based on the investigative research of the construction, implementation, and assessment of ideological and political education in the Cardiology curriculum at Tongji University, three main problems were concluded: the teaching methods were not suitable for the current needs of ideological and political construction in the curriculum; the professional knowledge teaching and ideological and political education were disconnected; and the quality of teaching evaluation was not high. The teaching team conducted detailed research and exploration through reforming the teaching mode, building an ideological and political material library and innovating the integration of ideological and political education with the curriculum, and innovating the evaluation system for the professional learning and ideological and political education of the curriculum, and designed an innovative method to implement curriculum ideology and politics based on material library refining combined with investigation feedback. Teaching practice verified that the method could effectively solve the three problems. The effectiveness monitoring after class demonstrated that the new method achieved the expected results, and the ideological and political construction of the Cardiology curriculum had significant improvements, proving that the method is practical and worth being promoted.

Abstract Gram-negative ( G-) bacteria, such as denitrifying bacteria and anaerobic ammonia oxidation bacteria, are highly social organisms capable of sophisticated cooperative behavior mediated via quorum sensing. As signal molecules of the chemical communication, N-acyl-homoserine lactones ( AHLs ) can mediate the quorum sensing of the functional microbial population and regulate the population density. To understand the growth of functional microbial population and the mechanism for biological nitrogen removal in upflow microaerobic sludge reactors ( UMSRs ) treating organic wastewater with low ratio of chemical oxygen demand to total nitrogen, a method was established to simultaneously detect AHLs in the microaerobic processes. Water-sludge mixtures sampled from the UMSRs were pretreated in sequence by liquid-liquid extraction using ethyl acetate, rotary evaporation, constant volume with methanol, separation by C18 column. Gradient elution was carried out using 5 mmol/L ammonium acetate ( containing 0 . 1% formic acid ) and methanol as mobile phases. On the base of multiple reaction monitoring analysis, a triple quadrupole mass spectrometer with an electrospray ionization was introduced to detect the target compounds. Nine kinds of AHLs were used to evaluate the established method and the results showed that the detection limits were 0 . 01-0 . 5 μg/L and all of the AHLs presented excellent linearity with the concentration ranging from 0 . 5 to 100 μg/L. The recovery and relative standard deviation ranged from 62. 5% to 118. 1% and 2. 9% to 12. 1%, respectively. The analysis could be finished within 6. 5 min. The rapid, accurate and precise method for detecting AHLs provided a new insight into the growth and metabolic activity of functional microbial population in the activated sludge processes to understand the mechanism of biological nitrogen removal, suggesting a good application in regulation and operation of wastewater biological treatment processes.

Objective:To explore the efficacy of traditional chinese medicine Danhong on renal pathological lesions of rats with early chronic kidney disease (CKD) and the role of transforming growth factorβ1(TGF‐β1) in it .Methods:Thirty male SD rats were divided into three groups :the early CKD group (model group) ,the sham‐operated group (control group) and Danhong treated group (treated group) ,with 10 in each group .Rats in the three groups were treated by uninephrectomy for building up early CKD model ,sham‐operation (separating tissues to renal capsule without kidney excision) ,and Danhong treatment after building up model ,respectively .Renal pathological lesions ,24 h urine protein excretion and renal function were observed .The concentration of TGF‐β1 in renal cortex and overall expression of TGF‐β1 in renal tissue was examined by enzyme‐linked immune‐sorbent assay (ELISA) and immunohistochemistry ,respectively .Results:Mild to moderate proliferation of glomeruli mesangial cells accompanied by broadened mesangium matrix ,glomeruli capsule wall adhesion and change of capillary wall , interstitial fibrosis and inflammatory monocytes infiltration was found in the model group other than the control group .Renal lesions were alleviated dramatically in treated group ,while compared to that in model group .The gross renal pathological score in model group was higher than that in control group (P<0 .05) ,however ,the score in treated group was lower than that in model group (P<0 .05) .The 24 h urinary protein excretion in model group and treated group was higher than that in control group (P<0 .01) ,while the 24 h urinary protein excretion in treated group was lower than that in model group (P<0 .01) . There was no significant difference among the three groups regarding blood creatinine level and urea level .Serum CysC levels in model group and treated group increased significantly than that in control group (P<0 .05) .The concentration of TGF‐β1 in renal cortex and overall expression of TGF‐β1 in renal tissue were higher in model group than those in control group(P<0 .05) ,while those in treated group were lower than those in model group (P<0 .05) .TGF‐β1 expression level in renal tissues was significantly associated with both the urinary protein excretion and the total renal pathological scores ( P< 0 .01 ) . Conclusions:Danhong alleviated renal pathological lesions by down‐regulating TGF‐β1 expression .

We expressed and prepared the recombinant fusion protein sTNFRII-gAD consisted of soluble TNF receptor II and the globular domain of adiponectin by Adenovirus Vector System in mammalian BHK21c022 cells. First we used the adenovirus vector containing EGFP gene (rAd5-EGFP) to infect BHK21c022 cells at different MOI (from 0 to 1 000), and then evaluated their transduction efficiency and cytotoxicity. Similarly, we constructed the replication-deficient adenovirus type 5-sTNFRII-gAD (rAd5-sTNFRII-gAD). We collected the supernatants for Western blotting to determine the optimal MOI by comparing the expression levels of sTNFRII-gAD fusion protein, 48 h after the BHK21c022 cells were infected by rAd5-sTNFRII-gAD at different MOIs (from 0 to 1 000). Then, we chose rAd5-sTNFRII-gAD at MOI 100 to infect five bottles of BHK21c022 cells in 100 mL of serum-free chemically defined media 100 mL, harvested the supernatant every 48 h for 6 times, and condense and purify sTNFRII-gAD fusion protein by ammonium sulfate salt-out and size-exclusion chromatography, respectively. Finally, we analyzed anti-TNFalpha activity of sTNFRII-gAD fusion protein on L929 cells in vitro. The results showed that the number of BHK21c022 cells expressing EGFP protein was increased significantly with the increase of MOI. However, some cells died at MOI of 1 000 while there was no significant cytotoxicity at MOI from 0 to 100. Western blotting analysis showed that the more adenoviruses, the higher expression of sTNFRII-gAD fusion protein in the supernatant with the highest expression at MOI 1 000. We successfully obtained about 11 mg bioactive and purified sTNFRII-gAD fusion protein at last. The in vitro assay demonstrated that the sTNFRII-gAD fusion protein was potent to antagonize TNFalpha's cytotoxicity to L929 cells. Put together, we established a recombinant adenovirus vector/BHK21 cell expression system, characteristic of the efficient serum-free culture and easy scaling-up.
Adenoviridae ; genetics ; metabolism ; Adiponectin ; biosynthesis ; genetics ; Animals ; Cell Line ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Receptors, Tumor Necrosis Factor, Type II ; biosynthesis ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics

Objective We aimed to describe the application value of continuous glucose monitoring system in patients with advanced gestational diabetes mellitus (GDM). Methods Pregant women in the medium and late pregant phases (24～35 weeks) underwent GDM screen test from January 2006 to April 2007. They first received 50 g glucose challenge test and 100g OGTT was performed 3 days later when the blood glucose was higher than or equal to 7.8mmol/L. According to the diagnostic criteria from American Diabetes Mellitus (ADA) 47 women were diagnosed to possess GDM and they were further divided into the test group (25 cases) and the control group (22 cases). The test group received 72 hours continuous glucose monitoring (CGMS). The control group adopted peripheral blood glucose monitoring using blood from the fingertip, 7 times per day. Results There were no records of consciousness hypoglycemic symptoms and hypoglycemia during monitoring. The CGMS data suggested that the record of the percent of high blood glucose was (17.5±3.1)%, percent of low blood glucose was (2.4±0.9)%, which were higher than those of the control group, which were (14.3±2.2)% and 0. Conclusions We recommend pregant women with GDM to undergo CGMS while using peripheral blood glucose monitoring with blood from the fingertip. It could systemicly evaluate the real control condition of blood glucose and ensure the safety of both mothers and babies.

OBJECTIVE: To study the changes of vestibular function in patients with diabetes mellitus and its clinical significance. METHOD: Electronystagmography (ENG) was used to examine 76 patients with diabetes mellitus and 60 healthy adults subjects. After clinical detection of vestibular function including spontaneous nystagmus, positional test, head shaking nystagmus, neck torsion test, caloric test, and sensory organization tests which consist of gaze, saccade and smooth pursuit test, the results of these two groups were recorded for qualitative and quantitative statistical analysis. RESULT: The rate of vestibular dysfunction in patients with diabetes mellitus were 68.4%. and that of the controls were 8.3%. There was significant difference between these two groups (chi2 = 15.472, P < 0.01). CONCLUSION Vertigo or dizziness occurred in patients with diabetes mellitus might be related to vestibular dysfunction. ENG test could be used as one of the objective clinical examinations in patients with diabetes mellitus.
Adult ; Aged ; Case-Control Studies ; Diabetes Mellitus ; physiopathology ; Electronystagmography ; Female ; Humans ; Male ; Middle Aged ; Nystagmus, Pathologic ; physiopathology ; Vertigo ; physiopathology