Batifiban, a synthetic cyclic peptide, is a potent platelet glycoprotein GPIIb/IIIa antagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects, and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55, 110, or 220 microg/kg, or multiple doses of an bolus followed intravenous infusion for 24 h (180 microg/kg plus 2.0 microg/min.kg, and 220 microg/kg plus 2.5 microg/min.kg) in this phase I clinical trial. Plasma levels of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma levels of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner, consistent with its mechanism as a GPIIb/IIIa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.
Injections, Intravenous ; Peptides, Cyclic/*pharmacokinetics ; Peptides, Cyclic/*pharmacology ; Platelet Aggregation Inhibitors/adverse effects ; Platelet Aggregation Inhibitors/*pharmacokinetics ; Platelet Aggregation Inhibitors/*pharmacology ; Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors ; Young Adult

This paper performs some explorations of the objective of talent-cultivation in 8-year-system medical education,and gives some advices of the objective of talent-cultivation in 8-year-system of Southern Medical University.

Objective To investigate the prevalence and progression process of atopic diseases in adolescents, and to assess their relationship with filaggrin(FLG)mutations. Methods Totally, 334 adolescents aged from 11 to 19 years in a middle school in shanghai were enrolled into this study. A clinical interview was carried out to determine the prevalence of atopic diseases (such as ichthyosis, atopic dermatitis (AD), asthma, rhinitis, etc)in these subjects. Peripheral blood samples were collected from 285 out of the 334 adolescents for screening for common FLG mutations, including 3321delA and K4671X. Five years later, these adolescents were followed up for reevaluation of clinical presentations of atopic diseases. Statistical analysis was carried out by the chi-square test with the SPSS 20.0 software. Results As the baseline survey showed, 19 (5.69%)of the 334 adolescents had AD, 14 (4.19%)had ichthyosis vulgaris, 36(10.78%)had allergic rhinitis, and 4(1.20%)had asthma. FLG mutations were observed in 24(8.42%) of the 285 adolescents. Five years later, 265 adoscents completed the follow-up, and 69 (20.66%)were lost to follow-up. Of the 265 adolescents reevaluated, 13(4.89%)had AD, 15(5.64%)had ichthyosis vulgaris, 27(10.15%)had allergic rhinitis, and 1 (0.38%)had asthma. By the time the second survey was performed, 6 out of the 19 patients initially diagnosed with AD had achieved complete regression, 13 had experienced a marked decrease in SCORing atopic dermatitis (SCORAD)score, and symptoms had disappeared in 9 of the 36 patients initially diagnosed with allergic rhinitis. The frequency of FLG mutations was 10.0%in patients with AD, 55.6%in those with ichthyosis, and 40.0%in those with both AD and ichthyosis, and the development of ichthyosis was associated with FLG mutations(P<0.001). Conclusions The frequency of common FLG mutations was 8.42%in these adolescents. FLG gene may be a semidominant gene associated with ichthyosis vulgaris, and multiple factors influence its expression.

Batifiban,a synthetic cyclic peptide,is a potent platelet glycoprotein GPⅡb/Ⅲa an-tagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects,and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55,110,or 220 μg/kg,or multiple doses of an bolus followed intravenous infusion for 24 h (180 μg/kg of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma lev-els of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner,consistent with its mechanism as a GP Ⅱb/Ⅲa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.

Objective The purpose of this study was to analyze the susceptibility profile of Acinetobacter baumannii to antimicrobial agents,and validate the results of different antimicrobial susceptibility testing methods,for improving the quality of antibiotic resistance monitoring data.Methods The susceptibility data of Hebei Provincial Antimicrobial Resistant Investigation Net were analyzed retrospectively and 126 strains ofA.baumannii were collected.The susceptibility ofA.baumannii to piperacillintazobactam,amikacin,gentamicin,ciprofloxacin,levofloxacin,ceftazidime,imipenem,and meropenem was tested by E-test,KirbyBauer method and VITEK system.Results The susceptibility results of the 126 A.baumannii strains showed that the susceptibility to piperacillin-tazobactam,amikacin,gentamicin,levofloxacin and ceftazidime was significantly different between the three methods (P＜0.05).The categorical agreement,major error,minor error,and very major error of Kirby-Bauer method were within acceptable range.There were evident difference in classification consistency for piperacillin-tazobactam,amikacin,levofloxacin between Kirby-Bauer method and VITEK (P＜0.05).Conclusions Different antimicrobial susceptibility testing methods may lead to different results of resistance monitoring data.Bias may be generated in antibiotic resistance surveillance if different methods are used.The susceptibility results of piperacillin-tazobactam,amikacin,levofloxacin derived from VITEK system should be validated by Kirby-Bauer or E-test method.

Objective:To investigate the anatomy of rectus femoris muscle flap and the anterolateral thigh muscle flap and their clinical application in reconstruction of large soft tissue defects after the removal of oral malignant tumour.Methods:From December 2006 to June 2009, 8 specimens of Chinese adult cadavers fixed in 10% formaldehyde were dissected to perform anatomy of anterolateral thigh region at the School of Basic Medical Sciences, Kunming Medical University. Anatomical images were analysed using Image-Pro Plus 6.0. Then, a retrospective study was performed on 19 patients who had postoperative defects after oral malignant tumour surgery and the defects were reconstructed with the rectus femoris muscle flap and the anterolateral thigh muscle flap from March 2020 to July 2022 at the Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital, Kunming Medical University. The postoperative defects of the 19 patients ranged from 3.0 cm×6.0 cm to 5.0 cm×10.0 cm. Ten rectus femoris muscle flaps, 8 anterolateral thigh muscle flaps and 1 combined rectus femoris muscle flap and anterolateral thigh muscle flap were used. The muscular flaps sized from 4.0 cm × 8.0 cm to 6.0 cm × 11.0 cm. Regular postoperative outpatient follow-ups were conducted.Results:The lengths of vessels of the harvested rectus femoris muscle flap and anterolateral thigh muscle flap were 63.4 mm± 12.9 mm and 112.5 mm± 19.6 mm, respectively. The starting outer diameters of the lateral circumflex thigh artery, the oblique branch of the lateral circumflex thigh artery and the descending branch of the lateral circumflex thigh artery were 2.92 mm±0.72 mm, 1.88 mm±0.23 mm and 2.29 mm±0.43 mm, respectively. Postoperative follow-up lasted for 7 to 32 months, with 17.5 months in average. Seventeen flaps were completely survived and the rectus femoris muscle flap was completely mucosalised 5 weeks after surgery. However, 2 rectus femoris muscle flaps had necrosis of which one was changed to a tongue flap reconstruction and the other encountered flap necrosis during postoperative radiotherapy and healed after debridement and dressing changes. There was no postoperative complication in the donor sites. Other than the 2 patients, all other 17 patients had satisfactory clinical outcomes.Conclusion:Both of the starting outer diameters and length of vessels of the femoris muscle flap and the anterolateral thigh muscle flap meet the requirements for reconstruction of maxillofacial defects, and both muscular flaps are simple to prepare, in good reconstructive results with few complication, as well as an excellent outcome. They are feasible approaches for reconstruction of large soft tissue defects left after the removal of an oral malignant tumour.

ObjectiveTo analyze the occurrence of suspected adverse events following immunization （AEFI） after changing the priority vaccination sites of the adsorbed acellular diphtherior-pertussis-tetanus vaccine （hereinafter referred to as DPT vaccine）， so as to provide scientific basis for mass vaccination. MethodsMonitoring data of AEFI for the DPT vaccine in Wujiang District from September 2020 to August 2022 were collected from China's disease prevention and control information system， and the vaccination information of DPT vaccine in all children's vaccination clinics in Wujiang District during the same period was selected. The incidence of AEFI for the DPT vaccine was analyzed and compared. ResultsThe reported incidence of AEFI was significantly lower in the buttocks than that in other sites （P<0.05）. The reported incidence of AEFI was significantly higher in booster immunization than that in basic immunization （P<0.05）. After inoculation at different sites， the main clinical symptoms of AEFI were local redness and swelling. There were significant differences in the incidence of local redness and swelling， local induration， pruritus and other symptoms （lethargy， abnormal crying， etc.） （P<0.05）. There were significant differences in the severity of local redness and swelling in different sites （P<0.05）. The degree of redness and swelling in the anterolateral thigh was lower than that in other sites （P<0.05）. The local strong reaction of swelling （>5.0 cm） in the deltoid muscle of the upper arm was significantly higher than that in the buttocks （P<0.05）. ConclusionThe DPT vaccine is safe in different parts of the body and is worth popularizing.

Background Zinc is a trace element essential for normal fetal heart development, and excess zinc can be toxic. The relationship between maternal and fetal zinc levels and the development of congenital heart disease (CHD) in the offspring is unclear. Objective To study the effects of maternal and neonatal zinc exposure levels on the risk of developing CHD in the offspring. Methods The data and biological samples of the study subjects were derived from the birth cohort established by Gansu Provincial Maternity and Child Care Hospital in Lanzhou from 2010 to 2012. Questionnaire surveys were conducted at baseline in the first trimester and at follow-up visits in the second trimester, the third trimester, and 42 d after delivery. Maternal venous blood during the third trimester and neonatal umbilical venous blood at delivery were collected, and information on their birth outcomes was extracted from medical records. Ninety-seven children with CHD diagnosed by echocardiography at birth and confirmed at the follow-up after 42 d were selected as the case group, and 194 healthy full-term infants were selected as the control group, 1∶2 matched for maternal age and geographical location from the database. The zinc concentrations in whole blood of pregnant mothers and umbilical cord blood of fetuses in both groups were measured by inductively coupled plasma mass spectrometry. According to the quartiles P₂₅ and P₇₅ of zinc levels in the whole blood of pregnant mothers and neonatal cord blood in the control group, zinc exposure was divided into three groups: low, medium, and high. After adjusting for maternal vaginal bleeding in early pregnancy, pre-pregnancy folic acid and vitamin supplementation, birth weight, and umbilical cerclage confounders, a multiple conditional logistic regression model was applied to analyze the associations between maternal whole blood and fetal umbilical cord blood zinc levels and the risk of CHD in the offspring, and a further subgroup analysis was performed by disease classification. Results The medians (P₂₅, P₇₅) of maternal whole blood zinc levels in the case group and the control group were 5.034 (3.456, 6.644) and 4.693 (3.411, 5.646) mg·L⁻¹, respectively, with significant differences between the two groups (P=0.029). The medians (P_25, P₇₅) of neonatal cord blood zinc level was 2.153 (1.479, 2.405) mg·L⁻¹ in the case group and 1.636 (1.304, 1.979) mg·L⁻¹ in the control group, with significant differences between the two groups (P<0.001). The zinc levels of maternal whole blood and neonatal cord blood in the simple CHD group were significantly higher than those in the control group (P<0.05). The multiple conditional logistic regression model showed that compared with the maternal medium zinc exposure level group (3.41-5.65 mg·L⁻¹), the risk of offspring CHD was 2.225 times of the high exposure level group (>5.65 mg·L⁻¹) (OR=2.225, 95%CI: 1.017-4.868). Compared with the neonatal medium zinc exposure level group (1.30-1.98 mg·L⁻¹), the neonatal high exposure level group (>1.98 mg·L⁻¹) also had an increased risk of CHD (OR=4.132, 95%CI: 1.801-9.480). The subgroup analysis results showed that compared with corresponding medium exposure level groups, the risk of simple CHD in the offspring of the maternal high zinc exposure level group was increased (OR=4.081, 95%CI: 1.427-11.669), and the risks of simple CHD (OR=7.122, 95%CI: 2.126-23.854) and complex CHD (OR=5.165, 95%CI: 1.859-14.346) of neonates of the neonatal high zinc exposure level group were increased. Conclusion Under the exposure levels of the study population, high concentrations of zinc exposure in pregnant mothers and neonates may be associated with the incidence of CHD.

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.
Humans ; COVID-19 ; Medicine, Chinese Traditional ; SARS-CoV-2 ; Critical Illness ; Treatment Outcome

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.