Diabetic retinopathy ( DR ) is one of the main blinding eye diseases for people over the age of 50, and diabetic macular edema ( DME) is the leading cause of vision loss is DR patients. The early diagnosis and early treatment is important. As OCT and FFA, mfERG, especially the retinal thickness, volume, retinal edema index quantitative indicators such as objective evaluation of macular edema, embodies the new progress of retinal imaging technology in recent years. OCT is a non -contact clinical application in recent years, noninvasive, high resolution of ophthalmic imaging examination, can do it on retinal ultrastructure observation and quantitative analysis, and the technology is relatively mature, become a routine inspection diagnosis of macular edema. Laser photocoagulation, intravitreous injection with Ranibizumab and vitrectomy is nowadays the important means for the treatment of intractable macular edema.

Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC₅₀) was 13.8 μmol·L^-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC₅₀: 41.99 μmol·L^-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

Objective To discuss the influence on peripheral circulation and oxygenation of different colloid osmotic pressure (COP) in pediatric cardiac surgery under cardiopulmonary bypass (CPB).Methods Sixty cases of non-cyanotic congenital heart disease patients under 10 kg were randomly selected and divided into 3 groups(n =20) according to the different COP level.COP values was adjusted by the ultrafiltration technique and colloid addition.The perioperative(T1-T6) arterial lactate level,different value between skin and rectal temperature,peripheral oxygen saturation (SpO2) and oxygenation index (OI) were observed in order to determine the different effect on peripheral circulation and oxygenation.Meanwhile,mechanical ventilation time and ICU time were recorded.Results The variation tendency of arterial lactate level was similar in each group,the value in the COP ＞ 18 mmHg (1 mmHg =0.133 kPa) group(group C) was significantly higher than COP 10-15 mmHg group (group A) and COP 16-18 mmHg group (group B) in T3 and T4,after CPB weaned,the values of Group A (1.25 ± 0.42) and Group C (1.33 ± 0.51) were higher than Group B (0.71 ± 0.29) at T6 point (P ＜ 0.05);the variation tendency of SpO2 was similar in each group too,the value of group C was significantly lower than group A and B at T5 point,the values of group A and C were significantly lower than group B at T6 point,P ＜ 0.05;the different value between skin and rectal temperature in group A was significantly higher than group B and C from T1 to T2 point(P ＜0.05),but not in T3 to T6 point;The minimal OI values of all the groups were appeared in T4 point,group B value was significantly higher than A and C in all time point,group C value was the lowest(P ＜0.05);the mechanical ventilation time in group B(2.13 ± 1.36) days and group C (2.93 ± 1.69) days were significantly lower than group A (3.83 ± 1.47) days,P ＜ 0.05.ICU time of group B (3.9 ± 1.1) days was significantly lower than group A (5.7 ± 2.5) days and C (6.0 ± 1.5) days.Conclusion During the pediatric CPB,the improper COP level will lead to bad oxygenation and poor peripheral circulation,got different prognosis ultimately.A reasonable COP level(16-18 mmHg) will do benefits to all the pediatric patients.

Animals ; Animals, Newborn ; Cells, Cultured ; Corticotropin-Releasing Hormone ; pharmacology ; Interleukin-6 ; metabolism ; Microglia ; cytology ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.

Ascorbic Acid ; therapeutic use ; Bandages ; Calcium Gluconate ; therapeutic use ; Humans ; Levofloxacin ; therapeutic use ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Sarcoidosis ; drug therapy ; Skin Ulcer ; drug therapy

Altitude ; Animals ; Arvicolinae ; Gene Expression ; Hypoxia ; Rats ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVE:To observe therapeutic efficacy and safety of Danshen chuanxiongqin injection combined with flunari-zine hydrochloride in the benign prevention and treatment of paroxysmal positional vertigo (BPPV) and lower extremity deep ve-nous thrombosis (DVT) in post-operative long-term bedridden patients with lower limb fractures. METHODS:300 post-operative long-term bedridden patients with lower limb fractures were selected and randomly divided into observation group and control group,with 150 cases in each group. Control group was given Flunarizine hydrochloride capsules orally 10 mg,qd;observation group was additionally given Danshen chuanxiongqin injection 10 ml+5% Glucose injection 250 ml,ivgtt,qd. The incidence of BPPV and DVT were observed in 2 groups after intervention,and the circumference of lower limb,blood coagulation indexes, blood rheology indexes and inflammatory factor were observed before and after intervention,and the incidence of ADR was com-pared. RESULTS:The incidence of BPPV and DVT in observation group were 18.0% and 16.7%,which were significantly lower than in control group(48.7% and 52.7%),with statistical significance(P<0.05);after intervention,the circumference of lower limb,blood rheology indexes and the levels of inflammatory factors in 2 groups were decreased significantly, while the coagula-tion indicators were significantly improved;the observation group was better than the control group,with statistical significance (P<0.05). There was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Danshen chuanxiongqin injection combined with flunarizine hydrochloride is effective in the prevention of BPPV and DVT in long-term bed-ridden patients with lower limb fractures,with low incidence of ADR.

Animals ; Antibodies, Monoclonal/pharmacology* ; Disease Models, Animal ; Interleukins/antagonists & inhibitors* ; Lupus Erythematosus, Systemic/therapy* ; Mice ; Mice, Inbred MRL lpr