AIMTo study the pharmacokinetic (PK) properties in rabbits treated with N-Ile(1)-Thr(2)-63-desulfato-r-hirudin (rH) newly developed in China by means of bioassay in order to provide preclinical experiment basis for its development as a novel anticoagulant agent.

METHODSrH plasma concentration was determined using bioassay based on ex vivo antithrombin activity of rH. Normal rabbits received iv rH 4.0, 2.0 and 1.0 mg/kg or sc rH 2.0 mg/kg, respectively. The rabbits with acute severe renal failure were given iv rH 2.0 mg/kg.

RESULTSThe bioassay described in this paper met requirements for study of PK in rabbits. The major PK parameters after iv dosing were as follows: t(1/2beta) 58.4-59 min. V(d) 0.09-0.12 L/kg, CL 0.0035-0.0040 L/(kg.min); AUC were proportional to the doses, t(1/2) and CL did not change significantly with the doses. The sc bioavailability reached 94%. The rabbits suffering from acute severe renal failure presented 11-fold longer t(1/2beta) and 13-fold greater AUC than normal healthy rabbits.

CONCLUSIONrH exhibited rapid elimination, distribution was only limited to extracellular space and good absorption from sc site. The excretion of rH by kidneys played a very important role in the elimination of rH. The PK of rH could be described by the two- and one-compartment model after iv and sc dosing, respectively, and followed linear kinetics.

Algorithms ; Animals ; Biological Assay ; methods ; Computer Simulation ; Hirudins ; blood ; pharmacokinetics ; Metabolic Clearance Rate ; Models, Biological ; Rabbits ; Reproducibility of Results ; Sensitivity and Specificity ; Thrombin Time ; methods

OBJECTIVETo clarify the significance of micrometastases in pelvic lymph nodes in patients with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP).

METHODSTwenty-one patients with clinically localized prostate cancer who received NHT between August 2007 and March 2010 were observed. The patients were clarified into four groups: pathological examination was positive (group A), real-time PCR examination targeting prostate specific antigen (PSA) mRNA and prostate specific membrane antigen (PSMA) mRNA were positive (group B), pathological examination and real-time PCR examination targeting PSA mRNA and PSMA mRNA were both negative (group C), and the control group (group D). After a standard bipedal lymphangiography the films were reviewed carefully by an experienced radiologist. If positive lymph nodes were seen or suspected, a thin-walled 22 gauge needle were directed transabdominally under fluoroscopic control into the area of question and an aspirate was obtained. The expression of PSA and PSMA in aspirate were assessed by a fully quantitative real-time PCR. The specimens were regarded in which either PSA mRNA or PSMA mRNA were positive as showing the "presence of micrometastasis". Lymph node specimens were also stained immunohistochemically with an antibody PSA after RP.

RESULTSPathological examination detected lymph node metastases from 3 cases, and real-time PCR further identified lymph node micrometastases from 14 cases with no pathological evidence of nodal involvement. The expression level of PSA mRNA and PSMA mRNA were statistically significant in patients with histological confirmed lymph node metastases and micrometastases detected by real-time PCR despite the lack of histological evidence, and the expression level of PSA mRNA and PSMA mRNA in aspirate were higher than the lymph node between the group A and group B.

CONCLUSIONSAlthough residual foci of atrophic prostate cancer cells in resected lymph nodes after NHT can be difficult to diagnose by pathological examination, the present results show the usefulness of quantitative real-time PCR targeting PSA and PSMA mRNA for detected micrometastatic tumour foci in pelvic lymph nodes from fine needle aspiration biopsy of lymph nodes before RP.

Aged ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Pelvis ; pathology ; Polymerase Chain Reaction ; methods ; Preoperative Care ; Prognosis ; Prostate-Specific Antigen ; genetics ; metabolism ; Prostatic Neoplasms ; pathology ; surgery ; RNA, Messenger ; genetics

Objective To investigate the effect of autologous tissue breast reconstruction with microsurgical lymph node transfers and lymphatic-venous anastomoses for the treatment of mastectomy related axillary cavitydeformation and upper extremity lymphedema .Methods The donor sites of lymph node transfers were mainly chosen according to the donor site of breast reconstruction .Themicrosurgical lymph nodes were transferred to the axillary cavity .When the superficial lymph vessels could be detected in lymphangiography with indocyanine green , thelymphatic-venous anastomoses were done to improve the lymphatic drainage .The treatment effect was assessed by the perimeter changes of different parts of upper extremity, the isotope lymphangiography and associated symptoms . Results 20 cases involved in autologous tissue breast reconstruction with microsurgical lymph node transfers , 18 cases from ingruinallymph nodes and 2 cases from lateral thoracic lymph nodes .2 cases receivedlymphatic-venous anastomoses on their upper extremity .The perimeters of palm and wrist were found significantly decreased in 6 months postoperation , while the perimeters of midpoint forearm and upper arm also decreased .The cellulitis, pain and swell happened less during the follow-up from 6 months up to 4 years. The postoperation isotope lymphangiography showed functional transferred lymph nodes inaxillary cavity , better lymphatic drainage and less volume of upper extremity .The subcutaneous superficial lymphatic drainage signs could be observed by the isotope lymphangiography in cases who had lymphatic -venous anastomoseson upper extremity .Conclusions Autologous tissue breast reconstruction with microsurgical lymph node transfers and lymphatic-venous anastomoses is a promising option for the treatment of mastectomy related axillary cavitydeformation and upper extremity lymphedema .The long term results need longer follow-up and more research .

Objective To investigate the effect of autologous tissue breast reconstruction with microsurgical lymph node transfers and lymphatic-venous anastomoses for the treatment of mastectomy related axillary cavitydeformation and upper extremity lymphedema .Methods The donor sites of lymph node transfers were mainly chosen according to the donor site of breast reconstruction .Themicrosurgical lymph nodes were transferred to the axillary cavity .When the superficial lymph vessels could be detected in lymphangiography with indocyanine green , thelymphatic-venous anastomoses were done to improve the lymphatic drainage .The treatment effect was assessed by the perimeter changes of different parts of upper extremity, the isotope lymphangiography and associated symptoms . Results 20 cases involved in autologous tissue breast reconstruction with microsurgical lymph node transfers , 18 cases from ingruinallymph nodes and 2 cases from lateral thoracic lymph nodes .2 cases receivedlymphatic-venous anastomoses on their upper extremity .The perimeters of palm and wrist were found significantly decreased in 6 months postoperation , while the perimeters of midpoint forearm and upper arm also decreased .The cellulitis, pain and swell happened less during the follow-up from 6 months up to 4 years. The postoperation isotope lymphangiography showed functional transferred lymph nodes inaxillary cavity , better lymphatic drainage and less volume of upper extremity .The subcutaneous superficial lymphatic drainage signs could be observed by the isotope lymphangiography in cases who had lymphatic -venous anastomoseson upper extremity .Conclusions Autologous tissue breast reconstruction with microsurgical lymph node transfers and lymphatic-venous anastomoses is a promising option for the treatment of mastectomy related axillary cavitydeformation and upper extremity lymphedema .The long term results need longer follow-up and more research .

A series of phthalimide-donepezil (PTA-DPZ) hybrids (5a-e, 6a-l) were designed, synthesized and evaluated as selective inhibitors of acetylcholinesterase (AChE). The results showed that some hybrids had strong AChE inhibitory activity with half maximal inhibitory concentration (IC₅₀) at nanomolar range, which was better than the control drugs galanthamine and tacrine, and equivalent to DPZ. Compound 6k exhibited the strongest inhibition to AChE with an IC₅₀ value of 0.13 μmol·L^-1. Kinetic and molecular modeling studies showed that 6k targeted both catalytic active site and peripheral anionic site of AChE. Moreover, some compounds could inhibit AChE-induced β-amyloid (Aβ) aggregation. In addition, absorption, distribution, metabolism and excretion prediction results showed 6k conforms to the Lipinski's rule of five and had high partition coefficient P value. These compounds, especially 6k, may be considered as a dual-functional lead compound for in-depth research.

Objective To investigate the effects on ribbon synapse of inner hair cells by superpulsed CO2 laser-assisted cochleostomy in SD rats.Methods Eighteen SD rats were randomly divided into the laser-assisted surgery groups (2 W group and 5 W group),the sham-operated group and the control group.Ten of those were performed a cochleostomy using superpulsed CO2 laser with corresponding power.Auditory brainstem responses (ABR) were measured pre-and postoperatively.The ribbon synapses at apical and middle cochlear turns were observed under laser scanning confocal microscope and then were quantified with 3ds Max software.Results The postoperative ABR thresholds of the 2 W and 5 W groups were larger than the preoperative cases (t =-5.65,P ＜ 0.01 ; t =-4.97,P ＜ 0.01).The synapse numbers at the middle turn decreased significantly in the 5 W group (F =17.15,P ＜ 0.01),while no significant changes were noted at the apical turn(P ＞0.05).There was no statistical difference in the 2 W group(P ＞0.05).Conclusions The superpulsed CO2 laser-assisted cochleostomy with high-power is accompanied by synaptic injury,while no obvious effects by the low-power laser surgery,which might be the safe strategy to preform cochleostomy.

Objective: This is a study to evaluate complication rate, satisfaction and quality of life after breast reconstruction under different classifications. The classification criteria are the timing of operation, surgical procedures, and patients′age. Methods: By reviewing the surgical cases from August 2004 to June 2018, the authors summarized the data of 102 patients with breast reconstruction of the same surgeon in Peking University People′s Hospital and Plastic Surgery Hospital (Institute) CAMS PUMC. Fifty-four patients who met the inclusion criteria and completed the BREAST-Q breast reconstruction module scale, were divided into immediate group or delayed group, according to the timing of operation; divided into abdomen group or other procedures group, according to the surgical procedure; and divided into the young patients′group or senior patients′group according to age. The index were (1) postoperative complication rate, (2)satisfaction with breasts, psychosocial well-being, physical well-being of chest and abdomen, sexual well-being, satisfaction with outcome, satisfaction with information, satisfaction with care (based on the BREAST-Q scale). Results: Complication rate was 9.1%(1/11) in the immediate group, 16.3%(7/43) in the delayed group, 14.7%(5/34) in the abdomen group, 15.0%(3/20) in other procedures group, 13.6%(3/22) in the young patients′group, and 15.6%(5/32) in the senior patients′group. There was no significant difference in the incidence of complications (P>0.05). The postoperative scores of satisfaction with breasts, psychological well-being and sexual well-being were significantly higher in the immediate group than in the delayed group(P=0.026, P<0.001 and P=0.001, respectively). The score of postoperative physical well-being of chest was significantly higher in the abdomen group than other procedures group(P=0.020). The score physical well-being of abdomen was lower compared with the preoperative in the abdomen group (P<0.001). The score of physical well-being of abdomen was lower in the senior patients′group than that of the young patients′group (P=0.010). Conclusions The complication incidence of breast reconstruction patients was similar among different groups. The breast reconstruction surgery can significantly improve satisfaction and quality of life of patients. To some extent, immediate breast reconstruction can reduce the psychological and physiological effects of breast loss on patients, leading to higher postoperative satisfaction. Breast reconstruction with abdominal flaps can provide patients with better chest health but poor abdomen health. Although elderly patients undergoing breast reconstruction will have poor physical well-being of abdomen, they can still achieve higher satisfaction of operation.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.