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 design ABC damage variable and positioning system for acetabular fracture and explore the feasibility and clinical practical value of the system through the multi-center analysis of 1122 acetabular fractures.

METHODSAccording to acetabular three-column conception, and pelvic ring lesions damage direction caused by acetabular fracture domino effect and injury degree of proximal femur joint, it defined class A as any column acetabular fracture; class B as any two-column acetabular fracture; class C as front, dome and posterior mixture acetabular fracture. Lower case English letters a, m, p represented front, dome, posterior fracture, respectively. Acetabular damage variables: 1 was simple displaced fractures; 2 was comminuted fractures; 3 was compression fractures. Pelvic ring lesions damage variables: alpha was sacroiliac joints or sacroiliac fracture horizontal separation deflection; beta was sacroiliac joints or sacroiliac fracture vertical separation deflection; gamma was pubic symphysis separation/superior and inferior ramus of pubis fracture deflection; alpha beta gamma delta was compound floating damage. Proximal humerus joint damage variables: I was femoral head fracture; II was femoral neck fracture; II was intertrochanteric fractures of femur; IV was I to III compound fracture. The ABC damage variable positioning system for acetabular fracture was made up by the above-mentioned variables. The statistics from March 1997 to February 2010 showed 1122 cases acetabular fractures with 18 cases of double side acetabular fracture and 1140 cases of acetabular fractures. The pelvics anterior-posterior view, ilium and obturator oblique view, and 2/3D-CT materials were analyzed and researched.

RESULTSEach damage variables distribution situation in 1140 cases of acetabular fracture involved A in 237 cases (20.8%), B in 605 cases (53.1%), C in 298 cases (26.1%);front column fracture in 808 cases(70.9%), dome fracture in 507 cases (44.5%), posterior fracture in 1026 cases (90%). Acetabular variables: variabe 1 in 203 cases of simple displaced fracture (17.8%); variabe 2 in 516 cases of comminuted fracture(45.3%); variabe 3 in 421 cases of compression fracture (36.9%); 249 cases of pelvic ring lesions damage (21.8%), 75 cases femoral head fracture (6.6%); 18 cases of double side acetabular fracture and relative pelvic ring and proximal humerus joint variables (1.58%). Key part and curative effect elements of 1140 cases acetabular fracture: 507 cases of dome or posterior acetabular fracture (44.5%); 421 cases of compression fracture (36.9%); 249 cases of pelvic ring variables (21.8%); 75 cases of proximal humerus joint variables (6.6%); 486 cases of simple Aa/pl/2,Bapl/2 acetabular fracture (42.6% ).

CONCLUSIONCompression fracture, especially defected compression fracture, takes important part in acetabular damage variables, and also presents that acetabular fracture with pelvic ring and proximal femoral damage variables are not rare at all. The relationship of the acetabular fracture damage variables, and its percentage shows the key points and elements in clinical treatment: weight-bearing to dome accounts for 44.5%; compression to defects account for 36.9%, pelvic ring to float accounts for 21.8%; dome fracture to double side fracture account for 6.6%. The system has significant guiding effects on clinic in terms of evaluation of injury severity, anatomic localization, difficulty index, alternative strategy, operative approach, effect of treatment,and prognosis. And the most important thing is that the system creates the comparison of damage variables in same type of fracture and the communication of homo-language and explores a new method.

Acetabulum ; injuries ; Adolescent ; Adult ; Aged ; Child ; Female ; Fractures, Bone ; classification ; diagnostic imaging ; Humans ; Male ; Medical Informatics ; methods ; Middle Aged ; Tomography, X-Ray Computed ; Young Adult

To explore the research hotspots and frontier directions of pyroptosis in the field of traditional Chinese medicine(TCM), the authors searched CNKI and Web of Science for literature related to pyroptosis in TCM, screened literature according to the search strategy and inclusion criteria, and analyzed the publication trend of the included literature. VOSviewer was used to draw author cooperation and keyword co-occurrence network diagrams, and CiteSpace was employed for keyword clustering, emergence, and timeline view. Finally, 507 Chinese literature and 464 English literature were included, and it was found that the number of Chinese and English literature was increasing rapidly year by year. The co-occurrence of the authors showed that in terms of Chinese literature, there was a representative research team composed of DU Guan-hua, WANG Shou-bao and FANG Lian-hua, and for English literature, the representative research team was composed of XIAO Xiao-he, BAI Zhao-fang and XU Guang. The network visualization of Chinese and English keywords revealed that inflammation, apoptosis, oxidative stress, autophagy, organ damage, fibrosis, atherosclerosis, and ischemia-reperfusion injury were the primary research diseases and pathological processes in TCM; berberine, resveratrol, puerarin, na-ringenin, astragaloside Ⅳ, and baicalin were the representative active ingredients; NLRP3/caspase-1/GSDMD, TLR4/NF-κB/NLRP3, and p38/MAPK signaling pathways were the main research pathways. Keyword clustering, emergence, and timeline analysis indicated that the pyroptosis research in TCM focused on the mechanism of TCM monomers and compounds intervening in diseases and pathological processes. Pyroptosis is a research hotspot in the area of TCM, and the current discussion mainly focuses on the mechanism of the therapeutic effect of TCM.
Pyroptosis ; Medicine, Chinese Traditional ; NLR Family, Pyrin Domain-Containing 3 Protein ; Pattern Recognition, Automated ; Apoptosis

During the coronavirus disease (COVID-19) epidemic, there have been concerns about the impact of vaccines on people's fertility, including the fertility of those who are currently preparing for pregnancy and those who might become pregnant in future. However, there is still a lack of research on the effect of the COVID-19 vaccine on male fertility, and it is not surprising that couples and donors have concerns regarding vaccination. In this study, a retrospective cohort study was conducted to examine semen quality before and after receipt of the inactivated COVID-19 vaccine. There were no statistically significant changes in semen parameters (volume, sperm concentration, progressive motility, and total progressive motile count) after two doses of vaccine (all P > 0.05). In summary, our study updates the most recent studies on the effects of the COVID-19 vaccine on male fertility, and the information from this study could be used to guide fertility recommendations for assisted reproductive technology (ART) patients and donors.
COVID-19 ; COVID-19 Vaccines ; Female ; Humans ; Male ; Pregnancy ; Retrospective Studies ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; Vaccination ; Vaccines, Inactivated