CD40 and its receptor CD40L are a very important pair of co-stimulating molecule in immune response, which have extensive biological effects. After stimulating CD40 signal, it can exert corresponding function through MAPK (JNK, ERK, p38) pathway, PI3K cascade, as well as NF-κB and STAT. The CD40 signal is closely related to tumor immunity, this moleculer has already become targeted-molecule for cancer treatment. Recently, there have been many anti-CD40 monoclonal antibodies displaying good anti-cancer effect, among which CHIR-12.12, SGN-40 and CP-870, 893 developed rapidly and successively have entered clinical research stage. This review focuses the status of anti-CD40 monoclonal antibody, including distribution of CD40, physiological function of CD40, CD40 and tumor immunity, anti-CD40 monoclonal antibodies and so on.
Animals ; Antibodies, Monoclonal ; CD40 Antigens ; immunology ; Humans ; Neoplasms

Adenomatous Polyposis Coli Protein ; genetics ; Chromatography, High Pressure Liquid ; methods ; Codon ; genetics ; DNA Mutational Analysis ; Fibromatosis, Aggressive ; genetics ; pathology ; Humans ; Mutation ; Polymerase Chain Reaction ; beta Catenin ; genetics

RT-PCR amplification of ginseng ?-amyrin synthase gene was successfully performed based on the total RNAs extracted from ginseng hairy roots induced by Agrobacterium rhizogenes A4 using a modified guanidine isothiocyanate-method. Sequence analysis of this gene revealed that its sequence was consistent with the sequence of a previously reported ginseng ?-amyrin synthase gene (GenBank No. AB009030). This gene was inserted into pMD-119T simple vector and transformed into E.coli DH5?. Furthermore antisense plant expression vector of this gene was constructed using the pBI121 vector, laying foundation for studies on antisense regulation of ginseng ?-amyrin synthase gene.

Genetic engineering is a powerful tool in Panax ginseng breeding.Genetic transformation and plant regeneration are the premise and foundation involved in genetic engineering of Panax ginseng.Ginseng can be regenerated through organogenesis or somatic embryogenesis and indirect somatic embryogenesis is mainly used for its regeneration.Summurized the factors influencing plant regeneration such as different explants,different carbohydrates,somatic embryo optimization and hormone-free approach.Ginseng transformation has been achieved by Agrobacterium tumefaciens and Agrobacterium rhizogenes and transgenic ginseng with good characters was obtained by introducing genes associated with biosynthesis of ginsenosides or herbicide gene.Hairy root culture system can supply large scale of ginsenosides,thus effect of rolC genes on ginseng hairy root induction,regeneration and bioreactor culture of hairy root were discussed.Additionally,problems that are present in genetic engineering of Panax ginseng were also discussed in this review.

Objective: To investigate the detection of HIV/AIDS cases in medical institutions in Tianjin Municipality from 2005 to 2021, so as to provide insights into optimization of HIV antibody testing strategies in medical institutions. Methods: All data pertaining to individuals receiving HIV antibody tests in medical institutions in Tianjin Municipality from 2005 to 2021 were collected from the information systems in medical institutions and the HIV/AIDS Prevention and Control Information System of Chinese Disease Prevention and Control Information System. The positive rate of HIV antibody and epidemiological characteristics of HIV/AIDS cases in medical institutions were analyzed. Results: The number of HIV antibody tests increased from 86 102 person-times in 2005 to 1 369 345 person-times in 2021 in medical institutions in Tianjin Municipality, with annual increase by 18.88%. The positive rate of HIV antibody increased from 2.44/104 to 2.85/104 (P<0.05), with annual increase by 2.79/104. Both the proportion of the number of HIV antibody tests and the number of HIV/AIDS cases detected by medical institutions in the whole city appeared a tendency towards a rise (P<0.05). A high positive rate of HIV antibody was seen in sexually transmitted disease clinics (53.69/104) and other testing services (12.25/104), and the highest positive rate of HIV antibody was seen in individuals at ages of 20 to 39 years (5.40/104), while the positive rate of HIV antibody was higher in men (5.84/104) than in women (0.53/104) (P<0.05). A total of 3 610 HIV/AIDS cases were detected in medical institutions in Tianjin Municipality from 2005 to 2021, with a median age of 38 (interquartile range, 24) years. Of all HIV/AIDS patients, there were 3 277 men (90.78%), and men who have sex with men was the predominant transmission route (63.46%), while the proportion of late identification of HIV/AIDS cases was 65.60%. In addition, the proportion of timely detection for the first CD4+T lymphocyte count testing increased from 23.81% in 2005 to 71.54% in 2021 (P<0.05). Conclusions The number of HIV antibody tests and positive rate of HIV antibody appeared a tendency towards a rise in medical institutions in Tianjin Municipality from 2005 to 2021. The HIV/AIDS cases were predominantly identified in sexually transmitted disease clinics and other testing services, and were predominantly men.

Objective: To understand characteristics of men who have sex with men (MSM) who applied for HIV antibody self-testing reagents through "AIDS self-testing" column of a WeChat official account named "Dark Blue Public Health Center" in Tianjin City, so as to provide insights into exploring online modes of HIV antibody self-testing for MSM. Methods: Data of MSM who were 18 years old or above, currently lived in Tianjin City, had sex with men in the past six months and applied for HIV antibody self-testing reagents through "AIDS self-testing" column from May 2018 to December 2022 were collected. Demographic characteristics, results return and positive findings were descriptively analyzed. Results: Data of 2 064 MSM were collected, including 1 052 MSM aged 20 to 29 years (50.97%), 1 522 unmarried MSM (73.74%), 545 workers (26.41%), 1 385 MSM with college education or above (67.10%), and 315 MSM without testing for HIV antibody in the past (15.26%). A total of 6 470 self-testing reagents were applied, and 5 942 testing results were returned, with a return rate of 91.84%. There were 33.28% (687/2 064) of the applicants applying for 66.32% (4 291/6 470) reagents multiple times. There were 73 MSM with positive results, accounting for 1.23%. Conclusions The MSM applying for HIV antibody self-testing reagents through "AIDS self-testing" are mainly young and highly educated, including some who have never tested for HIV. However, attention should be paid to duplicate applications and the return rate should be increased.

BACKGROUND:Piglitazone, aperoxisome proliferator-activated receptor γ(PPAR-γ) agonist, has been demonstrated topromote survivalandcardiac differentiation ofexogenous bone marrow mesenchymal stem celsto improvecardiacfunction.In this study, we attempted to investigate whether pioglitazone couldinduce cardiac differentiation of endogenous bone marrow mesenchymal stem celsandimprove cardiacfunction, andmeanwhile, probed into the relevant mechanisms.
OBJECTIVE:To compare the therapeutic efficacy ofpioglitazone combined with bone marrow mesenchymal stem cel transplantation, pioglitazone alone and phosphate buffer solution(PBS)and to investigatetherelevant mechanisms.
METHODS:ThirtySprague-Dawley ratswith myocardial infarctioninducedby ligation of the left anterior descending coronary artery were randomized intocombined group (combination of bone marrow mesenchymal stem cels and pioglitazone), pioglitazone group andPBSgroup. Two weeks later, PKH26-labeled bone marrow mesenchymal stem cels inPBSorPBSalone wereinjected into the local infarct zone in the combinedgroup andthe other twogroups, respectively. Pioglitazone (3 mg/kg/d) was given by the oral gavage in the combinedand pioglitazone groups forcontinuous2weeks after cels transplantation. At 2weeks after treatment, cardiac functions were evaluated. In addition, expressions of PPAR-γ, connexin 43 and relative factors in transforming growth factor-β1/SMAD signaling pathway were examined in different areas of the left ventricle from each harvested heart.
RESULTS AND CONCLUSION:There were no differences in the baseline parameters of cardiac function between the two groups.Twoweeksafter treatment, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and left ventricular ejection fraction were significantlyimprovedin the combined groupcompared with the other two groups; the expression of PPAR-γ was significantly increased in different zones of the left ventriclein the combined andpioglitazone groups.In the combined group, there was a significantlyhigher expression of connexin 43, and the levels of transforming growth factor-β1, SMAD2 and SMAD3 were obviously attenuated in the infarctand marginal zones.However, no differences were found in the abovedeterminants between the pioglitazone andPBSgroups. To conclude, pioglitazone cannot induce the differentiation andproliferation of endogenous bone marrow mesenchymal stem cels, but pioglitazone combined with exogenous bone marrow mesenchymal stem cels can improve cardiac function post myocardial infarction.In this process,PPAR-γmight promote the connexin 43 expression inexogenous bone marrow mesenchymal stem celsviathe blockade oftransforming growth factor-β1/SMAD signaling pathway.

BACKGROUND:Previous studies have demonstrated that the electrophysiological stability and ventricular fibril ation threshold after myocardial infarction in rats are significantly improved in the mid-term of cardiac stem cel transplantation, but relative regulatory mechanism and pathway remain unclear. OBJECTIVE:To explore the relative molecular regulatory mechanism of cardiac stem cel s improving the electrophysiological stability and ventricular fibril ation threshold after myocardial infarction in rats. METHODS:Myocardial infarction was induced in 20 Sprague-Dawley rats by ligation of the left anterior descending coronary, which were then randomized into two groups (n=10 per group) and were subjected to the injection of cardiac stem cel s labeled with PKH26 in phosphate buffer solution (cardiac stem cel group) or the same amount of phosphate buffer solution (PBS) alone (PBS group) into the local infarct zone at 2 weeks after modeling, respectively. Six weeks later, relevant signaling molecules involved in the ANGII/AT1R/TGF-β1/SMAD/Cx43 pathway were al examined in myocardial tissues of the left ventricle and harvested blood samples. RESULTS AND CONCLUSION:Compared with the PBS group, expressions of connexin 43 in different zones of the left ventricle were significantly increased in the cardiac stem cel group (P<0.01);there was a significant reduction of the angiotensin II level in plasma and different regions of the left ventricular (P<0.05;P<0.01). Furthermore, in the cardiac stem cel group, expressions of angiotensin II type I receptor, transforming growth factor-β1, SMAD2 and SMAD3 were significantly decreased (P<0.01). Whereas SMAD7 was significantly elevated (P<0.05) in different areas of the left ventricle compared with the phosphate buffer solution group. These findings suggest that the cardiac stem cel transplantation can improve the electrophysiological stability and ventricular fibril ation threshold after myocardial infarction by enhancing the expression of connexin 43 via ANGII/AT1R/TGF-beta1/SMAD/CX43 signaling pathway.

To investigate theological properties of common hydrophilic gel excipients such as Carbopol based on viscosity, the viscosity was determined by rotation method and falling-ball method. Linear regression was made between ln(eta) and concentration, the slope of which was used to explore the relation between viscosity and concentration of different excipients. The viscosity flow active energy (E(eta)) was calculated according to Arrhenius equation and was used to investigate the relation between viscosity and temperature of different excipients. The results showed that viscosities measured by two methods were consistent. Concentration of guargum (GG) and hydroxypropylmethyl cellulose (HPMC) solution had a great influence on the viscosity, k > 5; while concentration of polyvinylpyrrolidone-K30 (PVP-K30) and polyethylene glycol 6000 (PEG6000) exerted a less effect on viscosity, k < 0.2; viscosity flow active energy of different excipients were close, which ranged from 30 to 40 kJ x mol(-1). Therefore, theological properties study could provide the basis for application of excipients and establish a foundation for the research of relation between excipients structure, property and function.
Excipients ; chemistry ; Gels ; chemistry ; Polyethylene Glycols ; chemistry ; Polyvinyls ; chemistry ; Povidone ; chemistry ; Rheology ; Temperature ; Viscosity

Recombinant RGD-Hirudin ( r-RGD-Hirudin ) has double functions: anti-thrombin activity and anti-platelet aggregation activity. To identify these functions, the expression plasmid, RGD-Hirudin-pPIC9K, was constructed by inserting cDNA of RGD-hirudin in yeast expression vector pPIC9K. The high expression clone was gained after screening. This clone was fermented for 3 days. The r-RGD-hirudin was secreted into the culture. It was ultra-filtrated from culture supernatant, then after gel filtration chromatography and anion exchange chromatography, the purified r-RGD-hirudin was gained. Its purity was larger than 97% and its specific activity was 12 000 ATU/mg. The yield per liter culture of purified r-RGD-hirudin was 1 g and overall recovery yield was more than 75% . The purified r-RGD-hirudin was identified by reductive SDS-PAGE, anti-thrombin activity assay, anti-platelet aggregation assay, LC/MS and isoelectrofocusing assay. It is proved that r-RGD-Hirudin is ramification of wt-Hirudin and it has anti-thrombin activity and anti-platelet aggregation activity.
Animals ; Fermentation ; Hirudins ; biosynthesis ; genetics ; isolation & purification ; pharmacology ; Male ; Molecular Weight ; Pichia ; genetics ; Platelet Aggregation Inhibitors ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; biosynthesis ; isolation & purification ; pharmacology