AIM:To study the effect of Hand2 (one of basic helix-loop-helix proteins’ transcription factors) expression on the development of the cardiac tissues in the fetal rats from gestational diabetes mellitus ( GDM) parents, and to investigate the potential pathogenesis of GDM-induced congenital cardiac defects in rats.METHODS: The adult Spra-gue-Dawley female rats were randomly divided into blank control group (n=24), GDM group (n=30), negative control group ( n=30) and insulin intervened group ( n=30) .The GDM model was established by intraperitoneal injection of 2%streptozotocin (STZ, 40 mg/kg body weight) to the pregnant rats on the successive day.The rats in insulin intervened group were injected with intermediate-acting insulin in order to keep the fasting blood glucose in the normal range.The rats in negative control group were injected with citric acid-sodium citrate buffer solution in the same position.Blood glucose and body weight were examined every day 72 h after STZ injection.On E12, E15 and E19, the rats were anesthetized and the embryonic cardiac tissues were collected after caesarean section.The histopathological changes of the cardiac tissues were observed under microscope with HE staining.The expression of Hand2 was analyzed by the method of immunohisto-chemistry.The expression of Hand2 in the cardiac tissues at mRNA and protein levels was determined by real-time fluores-cence quantitative PCR and Western blotting.RESULTS:During the development of embryonic heart, the protein expres-sion of Hand2 in the cardiac tissues was showed dynamic changes.Observed on E12, obviously increased on E15, and at the highest level on E19.Compared with the other 3 groups, the protein and mRNA expression of Hand2 in GDM group was decreased at the time points of E12 and E15.CONCLUSION:The morbidity of fetal cardiac malformation is significantly increased in GDM group, suggesting that Hand2 may be involved in the development of cardiac malformation in GDM.

BACKGROUND: Scar hypertrophy is always followed by the wound healing in burn and trauma. Endothelial cells play a key role in scar hypertrophy, so inhibitory growth of endothelial cells can relieve scar hypertrophy to a certain degree. OBJECTIVE: To construct a recombinant adenovirus vector expressing human endostatin (Ad/hEnd), and to investigate the cooperative effect of Ad/hEnd and keratinocyte on endothelial cell proliferation. DESIGN, TIME AND SETTING: Observational study, which was performed in the State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital of the Third Military Medical University of Chinese PLA between September 2006 and May 2007. MATERIALS: pAdTrack-CMV and pAdEasy-1 were obtained from Stratagene Company, USA; 293 cell and Ecoli.DH5α were stored in our laboratory. METHODS: The endostatin gene sequence was obtained by reverse transcription-polymerase chain reaction (RT-PCR) and polymerase chain reaction (PCR) based on mRNA of human fetal hepatic tissue and inserted into the adenovims shuttle plasmid pAdTrack-CMV to obtain recombinant plasmid pAdTrack-ES. After identification, positive recon was transformed into pAdeasy 1 recipient virus to screen positive clones. The adenovirus Ad/hEnd was generated from 293 cells and identified by PCR and fluorescence microscope. Then the keratinocytes were infected with Ad/hEnd, and co-cultured with endothelial cells by nest dish culture method. The content of endostatin was detected, and the non-transfection keratinocytes were used as the controls. MAIN OUTCOME MEASURES: Homologous recombination and identification of pAd/hEnd; generation and identification of Ad/hEnd; endostatin expression after 293 cell transfection; purification and titer measurement of Ad/hEnd; content of endostatin in culture solution; apoptotic percentage of endothelial cells; inhibitory ratio of endothelial cells. RESULTS: Ad/hEnd was constructed and the virus titer was generally up to 1.65×1012 PFU/L. Ad/hEnd-infected keratinocytes could effectively express and secrete endostatin of which the content reached 226 μg/L after 3 days of co-culture. The apoptotic percentage and inhibitory ratio of the endothelial cells co-cultured with Ad/hEnd-infected keratinocytes were significantly higher than those in control group (P<0.05). CONCLUSION: Ad/hEnd-infected keratinocytes co-cultured with endothelial cells can promote apoptosis and inhibit proliferation of endothelial cells through excretion of endostatin.

OBJECTIVE: To explore the efficacy of individualized subcutaneous immunotherapy (SCIT) in allergic rhinitis(AR) maintain phase. METHOD: Compare nasal symptom scores (VAS) and special disease scale--nasal conjunctivitis quality of life questionnaire(RQLQ) score after 3 years treatment to evaluate the therapeutic effect of each group and the level of improving patients quality of life. Take patients' blood to detect the serum level of IL-10 by enzyme linked immunosorbent test (enzyme linked immunosorbent assay). RESULT: After 3 years treatment, there was no difference of VAS between the conventional SCIT group and the individualized SCIT group. ELISA results showed that the level of IL-10 was significantly higher in the drug symptomatic treatment group than that in the healthy group, the levels of IL-10 were significantly lower in the conventional SCIT group and the individualized SCIT group than that in the healthy group, but there was no difference between the conventional SCIT and the individualized SCIT group. CONCLUSION After 3 years treatment, there was no difference between conventional and individualized SCIT groups. But the efficacy of the conventional and individualized SCIT groups were significantly better than that in the drug symptomatic treatment group.
Desensitization, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Humans ; Injections, Subcutaneous ; Interleukin-10 ; blood ; Precision Medicine ; Quality of Life ; Rhinitis, Allergic ; drug therapy ; Surveys and Questionnaires

OBJECTIVE: To evaluate symptoms and quality of life in children with allergic rhinitis, and to evaluate the correlations among the skin prick tests results, symptoms and quality of life. METHOD: Visual analog scale (VAS) was used to assess the symptoms severity, rhinoconjunctivitis quality of life questionnaire (RQLQ) was used to assess quality of life, the skin prick tests results were recorded, and statistics analysis was carried out among them. RESULT: (1) There were significant differences among the five aspects of RQLQ (F = 32.03, P < 0.01), nasal symptoms aspect was the most affected aspect of quality of life, moreover, there were significant differences among all the items of RQLQ (F = 7.35, P < 0.01), the scores of nasal blockage, sneezing and rhinorrhea were the highest, there were no significant differences among them. (2) VAS was significantly correlated with RQLQ, moreover, the scores of unable to get to sleep and embarrassed by symptoms were significantly correlated with rhinorrhea VAS scores (r = 0.230, P < 0.05; r = 0.325, P < 0.01), the score of wake up during the night was significantly correlated with nasal itching and sneezing VAS scores (r = 0.385, P < 0.01; r = 0.231, P < 0.05), the score of can't concentrate was significantly correlated with the scores of unable to get to sleep and wake up during the night (r = 0.316, P < 0.01; r = 0.525, P < 0.01), the score of irritable was significantly correlated with the scores of unable to get to sleep (r = 0.243, P < 0.05). (3) The results of the skin prick tests were related with VAS and RQLQ. CONCLUSION Nasal symptoms severity may significantly correlated with the quality of life. Rhinorrhea, nasal itching and sneezing may be the main factors affecting the quality of sleep, while the quality of sleep may affect non-hay-fever symptoms and emotions, rhinorrhea may be the main factor affecting embarrassed by symptoms. The allergen level was related with the symptoms severity and quality of life.
Child ; Female ; Humans ; Male ; Quality of Life ; Rhinitis, Allergic, Perennial ; diagnosis ; Surveys and Questionnaires

To investigate the cellular immunogenicity of influenza vaccine liposomes dry powder using the film-dispersion and freeze-thawing. Mice were divided into the non-liposomal influenza vaccine group, film-dispersion prepared liposomal influenza vaccine group, freeze-thawing lyophilized influenza vaccine liposome group, positive control group and negative control group(n=5). 6 μg of hemagglutinin of H1N1 subtype per mouse was delivered tracheally to the mice of lyophilized liposomes groups, with the same dose for non-liposomes intraperitoneally delivered groups as the positive control, and PBS intraperotoneal injection group as the negative control. After 28-day of immunization, the proliferationofsplenic lymphocytes was detected by MTT assay; CD4+cell and CD8+cell were analyzed by flow cytometry. The dry powder of influenza vaccine liposomes prepared by the above two methods, both induce cellular immunity, with no significant difference in the induced on immunogenicity between the prepared products(P< 0. 05). The results showed that freeze-thawing method is feasible in the preparation of vaccine liposomes, leading to the attenuated live vaccine liposome preparation.

Objective:To explore the distribution of pathogenic bacteria during perioperative period of kidney transplantation(KT)patients and examine drug resistance of major clinical pathogens to commonly used antibiotics to provide references for empirical medication of pathogenic bacteria infection after KT.Methods:From January 1, 2020 to June 30, 2021, 251 patients undergoing deceased donation KT on kidney transplant ward were selected.Clinical samples were collected and distribution and drug resistance of pathogenic bacteria examined for analyzing the incidence of possible donor-derived infections and predicting prognoses.Results:The detection rate of pathogens was 12.18%(367/3 014). A total of 225 non-repetitive strains were isolated.Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 48.89%(110/225), 43.11%(97/225)and 8.00%(18/225). The proportion of lavage fluid in all isolated bacteria was 49.78%(112/225). And Staphylococcus epidermidis and Klebsiella pneumoniae predominated.Drainage fluid accounted for 24.88%(56/225)and Pseudomonas putida and Staphylococcus haemolyticus predominated.Urine accounted for 18.67%(42/225)with a dominance of Enterococcus faecium; blood accounted for 6.22%(14/225)with a dominance of S. epidermidis.All detected pathogens showed varying degrees of resistance.The resistance rates of E. faecium to ampicillin, vancomycin and linezolid were 93.33%(28/30), 6.45%(2/31)and 38.71%(12/31). The resistance rates of K. pneumoniae and Acinetobacter baumannii to carbapenems were 71.43%(20/28)and 80.00%(12/15). The incidence of possible donor-derived infection was 3.59%(9/251)and there was no mortality.Conclusions:The detection rate of pathogenic bacteria is high in KT patients during perioperative period.There is a diverse distribution of isolates of different specimen types and all detected pathogens show varying degrees of drug resistance.Clinicians should regularly analyze the distribution characteristics and causes of drug-resistant bacteria.And antibiotics should be optimized according to the results of drug sensitivity.

Objective To investigate the medical expense control model of rational drug use based on the China healthcare security diagnosis related groups(CHS-DRG)simulation in Beijing in 2021.Methods By analyzing the simulated operation data from January to March 2021 before the intervention,the groups with rational drug management improving potential among the top three surgical disease groups in terms of the number of cases enrolled in the surgical department were selected.Then,the targeted intervention and guidance were implemented to the selected disease groups.Finally,the analysis was obtained by comparing the changes in several key indicators such as the average drug cost,average antibacterial drug cost,average surplus and average length of stay during June to August 2021.Moreover,the differences in antimicrobial drug use intensity and hospital infection reporting of the department as a whole where the problematic groups were located were also investigated.Results Before the intervention,the otolaryngology related groups(including DD29 and DE19),urology surgery related groups(including LD19 and LJ13)could be improved in antibacterial drug use during the perioperative period.Meanwhile,the chest surgery related group(including EB19)had space to be improved in auxiliary medication.After the intervention,the five groups'average drug cost and average antibacterial drug cost in the otolaryngology and urology surgery departments are all decreased.The antibiotics use intensity is also declined in otolaryngology and urology surgery departments.The average surplus of otolaryngology and urology surgery related groups are increased,with the DE19 disease group in ENT also achieving a profit turnaround.As for the indicators related to the quality of care,there were no significant differences in the groups'average length of stay and nosocomial infection reporting of these departments.Conclusion The hospital operation based on CHS-DRG payment is both an opportunity and a challenge.The all-inclusive payment model has prompted hospitals to take the initiative in controlling costs,and the exploration of a rational medication management and cost-control model related to disease groups has begun to show results in terms of cost reductions without affecting the quality of medical care.The research can also provide a solid foundation for the CHS-DRG actual payment and sustainable development of medical insurance fund.

OBJECTIVE： To systematically evaluate the efficacy and safety of TCM compound preparation for tonifying kidney and activating blood circulation， and to provide evidence-based reference for rational drug use in the clinic. METHODS： By retrieving Cochrane library， PubMed， Embase， CBM， CNKI， VIP and Wanfang database， randomized controlled trials （RCTs） about TCM compound preparation for tonifying kidney and activating blood circulation （trial group） versus calcium or non-calcium agents （control group） in the treatment of postmenopausal osteoporosis were included. After literature screening， data extraction and quality evaluation with bias risk evaluation tool and Jadad scale of Cochrane system evaluator manual 5.1.0， Meta-analysis was conducted by using Stata 12.0 software， and trial sequential analysis （TSA） was conducted by using TSA 0.9 software. RESULTS： Totally 18 RCTs were included， involving 1 408 patients. The results of Meta-analysis showed that total response rate [RR＝1.35，95％CI（1.17，1.54），P＜0.000 1] and bone density[SMD＝0.24，95％CI（0.16，0.32），P＜0.000 1] of trial group were significantly higher than those of control group； blood calcium [SMD＝－0.05，95％CI（－0.09，0.00）， P＝0.033] of trial group was significantly lower than that of control group. There was no statistical significance in the levels of urine creatinine [SMD＝－1.60，95％CI（－5.94，2.74），P＝0.470]， urinary calcium/urine creatinine ratio [SMD＝－0.05，95％CI（－0.14，0.04），P＝0.295]， urinary hydroxyproline/urine creatinine ratio [SMD＝－0.16，95％CI（－1.04，0.72），P＝0.726]， ALT [SMD＝0.51，95％CI（－3.26，4.28），P＝0.790]， AST [SMD＝0.23，95％CI（－5.22，4.77），P＝0.929]， serum alkaline phosphatase [SMD＝－0.22，95％CI（－0.68，0.25），P＝0.361]， serum phosphate [SMD＝－0.02，95％CI（－0.11，0.07），P＝0.639]， urea nitrogen [SMD＝－0.19，95％CI（－0.70，0.31），P＝0.453]， estradiol [SMD＝0.62，95％CI（－0.28，1.52），P＝0.177]， IL-6 [SMD＝－1.78，95％CI（－4.86，1.30），P＝0.258] or VAS [SMD＝0.55，95％CI（－1.03，2.13），P＝0.496] between 2 groups. No server ADR was found in 2 groups. TSA showed that there were extract evidences for total response rate of TCM compound preparation in the treatment postmenopausal osteoporosis. CONCLUSIONS： TCM compound preparation for tonifying kidney and activating blood circulation shows significant therapeutic efficacy for postmenopausal osteoporosis， and can improve serum calcium and bone density with good safety.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.