Aim To study the effect of genistein on contractility of isolated papillary muscles in guinea pig and its mechanisms.Methods Isolated guinea pig papillary muscles were suspended in organ baths containing KH solution,and the effect of genistein on contractility of myocardium was observed after an equilibration period.Results Genistein and isoprenaline hydrochloride showed positive inotropic effects on contractility of myocardium in a dose-dependent manner(1～100 ?mol?L~(-1)) Propranolol(1 ?mol?L~(-1)) and verapamil hydrochloride(0.5 ?mol?L~(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride(2 ?mol?L~(-1)),but did not change the effect of genistein(100 ?mol?L~(-1)).Furthermore,the enhancement of the contractility induced by elevation of extracellular Ca~(2+) concentration in papillary muscles did not show any change after pretreatment with genistein(1,10 ?mol?L~(-1)).Finally,the positive inotropic effect of genistein was attenuated partially by tamoxifen(1 ?mol?L~(-1)),however,was not influenced by sodium orthovanadate(1 ?mol?L~(-1)).Conclusions Genistein has the positive inotropic effect on guinea pig papillary muscles,which is not related to the activation of Ca~(2+) channel on cell membrane,? adrenoceptor and tyrosine kinase pathway,but this effect may involve in uptake and utilization of sarcoplasmic reticulum Ca~(2+).

Objective To evaluate the feasibility of active breathing control (ABC) in conformal radiotherapy (CRT) for patients with non-small cell lung cancer (NSCLC). Methods From Feb 2005 to Mar 2008, 29 patients with inoperable NSCLC (stage Ⅱ-Ⅳ) were evaluated. For each patient, two series of CT scans were obtained with free breathing (FB) and ABC system during simulation, respectively. Then two confonnal radiotherapy (CRT) plans were finished based on the two sets of reconstructed images. The pattern of post-inspiratory breath-hold was triggered at 80% of the peak of inspiration curve. The margin of clinical target volume (CTV) to planning target volume (PTV) was 0. 6 cm for lesions of the superior lobe, and 1.0 cm for the lesions of middle and inferior lobes. Three to five coplanar fields were performed in conformal radiotherapy. The gross tumor volume (GTV), CTV, PTV, volume of the bilateral lungs (Volume_(lung)), V_(20) and mean lung dose (MLD) of two plans were evaluated by dose-volume histogram (DVH). The World Health Organization criteria and National Cancer Institute Common Toxicity Criteria 3.0 (NCI-CTC3.0) scale were used to assess the immediate response and acute side-effect, respectively. Results Significant differences of GTV, CTV, FIN, Volum_(lung), V_(20) and MDL were observed between the two plans (36. 35 cm~3 vs. 31.40 cm~3, t = 9. 70, P <0. 001 ;82. 33 cm~3 vs. 70. 83 cm~3, t = 8. 19, P < 0. 001 ; 230. 73 cm~3 vs. 197.59 cm~3 ,t=5.72,P <0. 001 ;21.66% vs. 18. 76% ,t = 11.16,P <0. 001 ;1329. 07 Gy vs. 1143. 14 Gy, t = 13. 24, P < 0. 001). With ABC, all patients completed their treatment successfully except one patient for financial problems. The median radiation dose to the GTV was 64 Gy (60 -64 Gy). The overall immediate response rate was 64% (18/28). According to the NCI-CTC 3.0, grade 1 and 2 acute radiation-related toxicities occurred in 68% (19/28) and 18% (5/28) of patients for esophagitis, 82% (23/28) and 7% (2/28) for pneumonitis, respectively. Grade 1, 2 and 3 bone marrow suppression occurred in 57% (16/28), 25% (7/28) and 14% (4/28) of patients, respectively. Grade 1 and 2 acute cardiac injuries occurred in 86% (24/28) and 14% (4/28) of patients. Conclusions During CRT for patients with NSCLC, the use of ABC can decrease the radiation dose and acute complications of normal tissues.

Objective To evaluate liver surgery (liver resection,liver transplantation,liver trauma) in patients with perioperative application of recombinant human growth hormone (rhGH) efficacy and safety.Methods We searched China biomedical literature database (CBM) and relevant randomized controlled Wanfang medicine,PubMed,Cochrane Library and Embase database to January 2018,application of rhGH for patients with liver surgery in rhGH,with placebo or blank control.According to certain criteria,the literatures were excluded and analyzed by RevMan 5.3 software.Results Total of 13 articles and 525 patients were included.The results showed that rhGH can improve the serum albumin (Alb),prealbumin (PA),transferrin (TF) synthesis [WMD =2.42,95％CI (0.45,4.40),P＜0.05;WMD =28.44,95％CI (17.70,39.17),P＜0.05;WMD=0.52,95％CI (0.44,0.61),P＜0.05];high level of CD4/CD8 [WMD =0.40,95％CI (0.22,0.58),P＜0.05];reduce the infection rate [RR=0.49,95％CI (0.31,0.77),P＜0.05];shorten the hospitalization time [WMD=-3.19,95％CI (-5.77,-0.61),P＜0.05];and will not increase the acute rejection and tumor recurrence rate,but need more exogenous insulin to control blood glucose.Conclusion Patients with perioperative application of rhGH can improve the nutrition status and immune function,reduce the rate of infection,promote the rehabilitation of patients,shorten the hospitalization time,and will not increase the acute rejection and tumor recurrence rate.

Objective:To resolve the issue of poor automatic segmentation of the bowel in women with pelvic tumors, a Dense V-Network model was established, trained and evaluated to accurately and automatically delineate the bowel of female patients with pelvic tumors.Methods:Dense Net and V-Net network models were combined to develop a Dense V-Network algorithm for automatic segmentation of 3D CT images. CT data were collected from 160 patients with cervical cancer, 130 of which were randomly selected as the training set to adjust the model parameters, and the remaining 30 were used as test set to evaluate the effect of automatic segmentation.Results:Eight parameters including Dice similarity coefficient (DSC) were utilized to quantitatively evaluate the segmentation effect. The DSC value, JD, ΔV, SI, IncI, HD (cm), MDA (mm), and DC (mm) of the small intestine were 0.86±0.03, 0.25±0.04, 0.10±0.07, 0.88±0.05, 0.85±0.05, 2.98±0.61, 2.40±0.45 and 4.13±1.74, which were better than those of any other single algorithm.Conclusion:Dense V-Network algorithm proposed in this paper can deliver accurate segmentation of the bowel organs. It can be applied in clinical practice after slight revision by physicians.

Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment, nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects. Nanomedicines hold tremendous theranostic potential for treating, monitoring, diagnosing, and controlling various diseases and are attracting an unfathomable amount of input of research resources. Against the backdrop of an exponentially growing number of publications, it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines. Herein, this review elaborates on the development trends of nanomedicines, emerging nanocarriers, in vivo fate and safety of nanomedicines, and their extensive applications. Moreover, the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed. The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.

Objective:To explore the feasibility and efficacy of subpatellar artery balloon molding in the treatment of diabetic foot ulcer caused by arterial ischemia.Methods:The clinical data of patients with diabetic foot ulcer caused by subpatellar artery disease treated in Xuanwu Hospital of Capital Medical University from December 2020 to April 2022 were retrospectively analyzed. Among them, 29 patients received medical balloon dilatation (drug balloon group) and 30 patients received balloon dilatation alone (simple balloon group). The improvement of lower limb ischemia at 3 and 6 months after surgery was analyzed in the two groups. The observation indicators included case-fatality rate, limb preservation rate, ulcer healing, Rutherford grading and pain score.Results:There was no significant difference in preoperative Rutherford grading between the two groups ( P>0.05). Three and six months after operation, the Rutherford grading in both groups was significantly improved compared with that before surgery (all P<0.05), and there was no statistical significance between the two groups ( P>0.05). There was no significant difference in preoperative pain scores between the two groups ( P>0.05). The pain scores of both groups were significantly decreased 3 and 6 months after surgery ( P<0.05), and there was no statistical significance between the two groups ( P>0.05). Three and six months after surgery, the wound ulcer healing rate in the drug balloon group was higher than that in the simple balloon group [51.7%(15/29) vs 43.3%(13/30), P=0.519; 86.2%(25/29) vs 50.0%(15/30), P=0.002]. There was no death or amputation in the two groups 3 and 6 months after surgery. Conclusions:Balloon dilatation can improve severe limb ischemia of diabetic foot. Compared with balloon dilatation alone, drug balloon dilatation is more beneficial to the healing of ulcer wounds in diabetic limb ischemia patients.

Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes, oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract, difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for oral drug delivery. This review provides an overview of the challenges and current approaches toward the oral delivery of liposomes.

Proteins and peptides (PPs) have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy, but fewer side effects. Owing to the poor stability and limited permeability through gastrointestinal (GI) tract and epithelia, the therapeutic PPs are usually administered by parenteral route. Given the big demand for oral administration in clinical use, a variety of researches focused on developing new technologies to overcome GI barriers of PPs, such as enteric coating, enzyme inhibitors, permeation enhancers, nanoparticles, as well as intestinal microdevices. Some new technologies have been developed under clinical trials and even on the market. This review summarizes the history, the physiological barriers and the overcoming approaches, current clinical and preclinical technologies, and future prospects of oral delivery of PPs.

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.