OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

Patients with traumatic brain injury (TBI) may develop neurological complications such as Alzheimer′s disease, stroke and epilepsy, which severely affect their quality of life. Currently, neurological complications after TBI are poorly understood and there are no comprehensive treatments or definitive interventions for them. Complex pathophysiological changes in the brain, systemic immunological responses, and gastrointestinal dysfunction after TBI all severely affect the biodiversity of the intestinal microbiota and related metabolites, which leads to intestinal dysbiosis and metabolic disorders and exert continued effects on the nervous system. Intestinal microbial probiotic flora that colonize in living organisms are a category of active microorganisms beneficial to the host and supplementation of intestinal probiotics can have a modulatory effect on the nervous system directly or indirectly. The targeted therapeutic effects of intestinal microbial probiotic flora on neurological complications after TBI and the intrinsic mechanism of the effects have not been comprehensively summarized currently. For this purpose, the authors reviewed the research progress on the effects of regulating intestinal microbial probiotic flora on post-TBI neurological complications so as to provide a reference for the clinical prevention and treatment of post-TBI neurological complications.

Objective To observe the effect of Qixian Tongluo Formula on contralateral corticospinal tract(CST)remodeling and motor functional recovery in rats with cerebral infarction,and to explore its potential molecular mechanism from the perspective of regulating factors related to never remodeling.Methods The rat middle cerebral artery occlusion(MCAO)model was established by silk thread ligation.Fifty model rats were randomly divided into model group,citicoline group(0.054 g·kg-1),Qixian Tongluo Formula low-,medium-and high-dose(7.83,15.66,31.32 g·kg-1)groups,and sham operation group,with 10 rats in each group.The intervention administration was started on the 3rd day after operation once a day for 26 consecutive days.On the 3rd,14th and 28th day after operation,the gross motor function was evaluated by Longa score,and the fine motor function was evaluated by beam-walking test(BWT)score.The contralateral motor cortex was injected with the nerve tracer biotin dextran amine(BDA)on the 14 th day after operation to anterogradely trace the CST.On the 28th day after operation,the expression of axonal growth associated protein-43(GAP-43)and BDA positive fibers in the contralateral motor cortex and cervical spinal cord were detected by immunohistochemistry.The co-localization areas of BDA positive fibers and presynaptic marker protein vesicular glutamate transporter 1(VGLUT1)in the cervical spinal cord gray matter were detected by immunofluorescence.The expressions of brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and nerve remodeling-associated inhibitory factor[Nogo-A,oligodendrocyte myelin glycoprotein(OMgp)and myelin-associated glycoprotein(MAG)]in the contralateral motor cortex were detected by Western Blot.Pearson correlation analysis was used to analyze the correlation between Longa score or BWT score and BDA/VGLUT1 co-localization area,respectively.Results Compared with the sham operation group,rats in the model group had obvious symptoms of motor function deficits,and the Longa scores were significantly increased(P＜0.01)and the BWT scores were significantly decreased(P＜0.05,P＜0.01)at each time point.The expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was up-regulated(P＜0.05),the number of edge-crossing fibers from the posterior funiculus in cervical cord was increased(P＜0.05),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was increased(P＜0.05),the expressions of BDNF,GDNF and NGF in the contralateral motor cortex were up-regulated(P＜0.05),while the expressions of Nogo-A,OMgp and MAG were down-regulated(P＜0.05).Compared with the model group,the Longa scores in each administration group on the 14th and 28th day after MCAO operation were significantly decreased(P＜0.01),the BWT scores were significantly increased(P＜0.01),the expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was significantly up-regulated(P＜0.01).The number of edge-crossing fibers from the posterior funiculus in cervical cord was significantly increased(P＜0.01),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was significantly increased(P＜0.01).The expressions of BDNF,GDNF and NGF in the contralateral motor cortex were significantly up-regulated(P＜0.01,P＜0.05),while the expressions of Nogo-A,OMgp and MAG were significantly down-regulated(P＜0.05),and the most significant effect was observed in the high dose group.The Longa score was negatively correlated with the co-localization area of BDA/VGLUT1(r=-0.89,P＜0.01),and the BWT score was positively correlated with the co-localization area of BDA/VGLUT1(r=0.84,P＜0.01).Conclusion Qixian Tongluo Formula can improve motor function through promoting contralateral CST remodeling in MCAO rats after cerebral infarction,and the molecular mechanism may be related to the regulation of the expression of nerve remodeling-associated factor in the contralateral motor cortex.

Objective:To compare the effect of neoadjuvant chemotherapy vs. concurrent chemoradiotherapy on the target volume and organs at risk for locally advanced bulky (>4 cm) cervical cancer. Methods:From March 1, 2019 to June 30, 2021, 146 patients pathologically diagnosed with cervical cancer were selected and randomly divided into two groups using random number table method: the neoadjuvant chemotherapy (NACT) + concurrent chemoradiotherapy (CCRT) group ( n=73) and CCRT group ( n=73). Patients in the NACT+CCRT group received 2 cycles of paclitaxel combined with cisplatin NACT, followed by CCRT, the chemotherapy regimen was the same as NACT. In the CCRT group, CCRT was given. Statistical description of categorical data was expressed by rate. The measurement data between two groups were compared by Wilcoxon rank-sum test for comparison of two independent samples, and the rate or composition ratio of two groups was compared by χ2 test. Results:Before radiotherapy, GTV in the NACT+CCRT group was (31.95±25.96) cm 3, significantly lower than (71.54±33.59) cm 3 in the CCRT group ( P<0.01). Besides, CTV and PTV in the NACT+CCRT group were also significantly lower compared with those in the CCRT group (both P<0.05). In terms of target volume dosimetry, D 100GTV, D 95CTV, V 100GTV, V 100CTV and V 95PTV in the NACT+CCRT group were significantly higher than those in the CCRT group (all P<0.05). The complete remision (CR) rates in the NACT+CCRT and CCRT groups were 86.3% and 67.6%, with statistical significance between two groups ( P<0.01) . Regarding organs at risk, NACT+CCRT group significantly reduced the dose to the bladder, rectum, small intestine and urethra compared with CCRT group (all P<0.05). Conclusions:NACT can reduce the volume of tumors in patients with large cervical masses, increase the radiation dose to tumors, reduce the dose to organs at risk, and make the three-dimensional brachytherapy easier. Therefore, NACT combined with CCRT may be a new choice for patients with locally advanced cervical cancer with large masses.

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.

Objective:To investigate the optimal bladder filling volume in the 3D brachytherapy of postoperative cervical cancer.Methods:Totally 111 early cervical cancer patients with positive incisal margins or insufficient safety boundaries were included. The normal saline 50, 60, 70, 80, 90, and 100 ml were filled into their bladders, and accordingly six groups were determined, and 66, 69, 66, 69, 72, 56 person-times in each group, respectively. The CT-based simulation positioning was performed. According to the ICRU 89 report, high-risk clinical target volume and organs at risk such as bladder and rectum were delineated. The Oncentra planning system was used to prepare the treatment program. The high-risk clinical target volume (HR-CTV), D90, and the D2 cm 3 and D1 cm 3 of organs at risk under different volumes were recorded. Results:Compared to the 60 ml group, the volume and dosage of HR-CTV in the groups of 50, 70, 80, 90, and 100 ml had no significant difference ( P>0.05). The D2 cm 3 and D1 cm 3 of the bladder and rectum of patients in these groups significantly decreased, and the difference was statistically significant ( tbladder = 3.21, 5.83, 2.89, 12.95, 7.96, Pbladder = 0.031, 0.010, 0.041, 0.000, 0.001; trectum = 2.94, 4.66, 2.53, 5.89, 4.13, Prectum = 0.037, 0.024, 0.049, 0.005, 0.028). The pairwise comparison among these groups except for the 60 ml group showed that the volume and dosage of HR-CTV and the D2 cm 3 and D1 cm 3 of bladder and rectum had no significant difference ( P > 0.05). Moreover, the D2 cm 3 and D1 cm 3 of sigmoid colon and small intestine of these groups had no significant difference ( P > 0.05). Conclusions:In the 3D brachytherapy of postoperative early cervical cancer, a bladder filling volume of 60 ml can ensure the volume and dose of HR-CTV and can protect the bladder and rectum compared with other filling volumes.

Objective:To systematically review the life experience of patients after bariatric and metabolic surgery.Methods:We searched PubMed, Web of Science, Embase, China National Knowledge Infrastructure, WanFang Data, and VIP by computer, and included qualitative research on the life experience of patients after bariatric and metabolic surgery. The retrieval time was from the establishment of the database to July 31, 2020. The quality of the included article was assessed using the quality evaluation criteria for qualitative research of the Australian Joanna Briggs Institute Evidence-Based Health Care Center (2017) . Meta-synthesis was performed using a pooled integration approach.Results:A total of 17 articles were included.A total of 38 themes were refined and grouped into 14 categories, resulting in four research results, namely return to normality, negative experience, control, and fear of isolation.Conclusions:The life experience of patients after bariatric surgery is complex and individual, and various experiences interact with each other, not a single existence. It is suggested that medical and nursing staff should pay attention to patients from multiple angles after surgery, establish a multidisciplinary follow-up team and diversified follow-up methods, and solve the multi-level needs of patients.

Objective:To understand the rotavirus contamination in the environment of microbiology laboratory, identify the key parts prone to contamination in the laboratory, and evaluate the inactivation efficacy of three common disinfectants on rotavirus.Methods:The laboratory environment and the surface of personal protective equipment were sampled with virus sampling swab after the experimental operation, and rotavirus nucleic acid was detected by real-time RT-PCR. Rotavirus inactivation experiments were carried out on chlorine containing disinfectant, ethanol and benzalkonium chloride according to the Chinese Technical Standard of Disinfection (2002 version).Results:A total of 174 samples were collected and 13 rotavirus nucleic acid positive samples were detected. The overall positive rate was 7.47%. The rotavirus could be inactivated with more than 4.00 log titer reduction, with 500 mg/L sodium hypochlorite disinfectant for 5 minutes, 75% ethanol for 1 minute and 1 500 mg/L benzalkonium chloride for 1 minute.Conclusions:There is a risk of rotavirus contamination in the microbiology laboratory. Sodium hypochlorite, ethanol and benzalkonium chloride disinfectants can effectively inactivate rotavirus and can be used for rotavirus decontamination.

Objective:To observe the morphological changes of the deep lumbar multifidus (DM) during rest and movement among persons with chronic low back pain (cLBP) using ultrasound imaging.Methods:Twenty-one cLBP patients and 30 pain-free healthy controls were studied. The resting thickness of the DM muscle was measured, and then its cross-sectional area and thickness during maximum voluntary isometric contraction (MVIC). The results were correlated with pain intensity and duration.Results:The cLBP patients showed significant reductions in the DM′s resting thickness, and in its cross-sectional area and thickness during a MVIC compared with the healthy controls. The resting thickness of the DM was positively correlated with pain duration, but not with pain intensity.Conclusions:These results suggest that cLBP patients have atrophy and less thickness change during an MVIC. This should be considered in planning clinical rehabilitation training.

The outbreaks caused by coronavirus (CoV) infections including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and COVID-19 have emerged in recent years, posing a continued threat to public health. Highly pathogenic CoV infections usually induce a series of immune responses, including innate immunity, humoral immunity, cellular immunity and mucosal immunity. These responses not only are critical to suppressing and eliminating the invasion of viruses, but also play an important role in immunopathological changes and disease progression. A deep understanding of the dual roles of immune responses will help to elucidate the pathogenic mechanism of CoV and maintain the balance between immune protection and immunopathology, which will be conducive to the research and development of safe and effective CoV vaccines. This review summarized the dual roles of immune responses in highly pathogenic CoV infections and discussed the implications for the research and development of novel CoV vaccines.