Objective To explore the clinical diagnostic value of quantitative detection of the slit homologue 2 (SLIT2) methylation for cervical high grade precancerous lesions. Methods According to histopathologic diagnostic results, 178 patients infected with high-risk HPV were divided into normal cervix group (n=45), low-grade lesion group (n=50) and high-grade lesion group (n=83). The cervical exfoliated cells were collected in three groups. The methylation levels of SLIT2 were measured by pyrosequencing in three groups. The diagnostic threshold of SLIT2 in high grade precancerous lesions was estimated by receiver operating characteristic (ROC) curve. Results The percentages of SLIT2 methylation were (4.53 ± 1.37)%, (5.81 ± 2.26)% and (11.80 ± 8.47)% in normal cervix group, low-grade lesion group and high-grade lesion group, respectively. And the differences between three groups were statistically significant (F=27.61, P<0.001). The percentage of SLIT2 methylation was significantly higher in high-grade lesion group than that of normal cervix group and low-grade lesion group (P<0.001). There was no significant difference in the percentage of SLIT2 methylation between normal cervix group and low-grade lesion group (P=0.297). The area under the ROC curve was 0.895 and optimal cut-off value was 6.41%. The sensitivity and specificity were 80.7% and 83.2%, respectively for the detection by SLIT2 methylation. Conclusion The quantitative detection of SLIT2 gene methylation level in cervical exfoliated cells by pyrosequencing can effectively diagnose cervical high grade precancerous lesions.

AIM: To study the immune regulation of paecilomyces cicadidae total polysaccharides. METHODS: After subcutaneous injection with 200 mg/L paecilomyces cicadidae total polysaccharides in the back of the rats for 17 days, the white blood cell (WBC) counts, and the levels of lipid peroxide (LPO) and reduced glutathione (GSH) in the spleen and thymus of rats were detected. The alveolar macrophages (AM?) cultured with 10% fetal bovine serum-RPMI-1640 for 2 h in vitro , then the activity of lactate dehydrogenase (LDH) and acid phosphatase (ACP) were detected by automatic biochemistry analyzer, and the ability devouring neutral red in the AM? were examined. RESULTS: Compared with control group, the WBC, the levels of GSH in the spleen and thymus, and the activities of LDH and ACP were significantly increased and the ability of devouring neutral red was also strengthened( P

AIM: To explore the immunomodulatory effect of paecilomyces cicadidae polysaccharides (PCPS).METHODS: Subcutaneous injection with 50, l00, 200 mg/kg of PCPS were given in the back of the rats everyday for l5 days. The number of white blood cells (WBC) was counted. The activities of acid phosphatase (ACP) and lactase dehydrogenase (LDH)in liver, kidney, spleen and thymus were detected by automatic biochemistry analyzer. The ability of devouring neutral red and activity of ACP, LDH, arginase in alveolar macrophages were also detected. The body weight of the rat everyday during experiment and weight of the spleen and thymus after the rats were killed were measured and wet weight index was calculated.RESULTS: The wet weight index of spleen and thymus, the activity of ACP, LDH, arginase and ability of devouring neutral red in alveolar macrophages in the test group treated with PCPS were significantly higher than those in control group. CONCLUSION: PCPS shows a significant immunomodulatory effect with the increasing counts of WBC and activation of alveolar macrophages in a dose-dependent manner.

Objective To evaluate the efficacy of Six Sigma management for shortening the waiting time of outpatients accepting radiography and improving patient satisfaction. Methods Six Sigma management was applied to identify the key points critical to quality in the process of radiography,analyze the factors influencing the waiting time,and take targeted measures to modify the process. Results The waiting time of patients accepting radiography was reduced by an average of 25.2min and the rate of dissatisfaction was decreased by 18%. Conclusion The application of Six Sigma management can effectively shorten the waiting time of outpatients accepting radiography and increase patient satisfaction.

AIM: To study the activation effects of maize pollen polysaccharides(PPM) on human thoracic cavity macrophage (hTM). METHODS: Activities of lactate dehydrogenase(LDH) and acid phosphatase (ACP) in the hTM were detected by automatic biochemical analyzer, and the level of tumor necrosis factor alpha(TNF-?) and interleukin-6(IL-6) in the hTM was analyzed by radioimmunoassay, after hTM were cultured with 0.312,0.625, 1.250, 2.500, 5.000 mg/mL PPM-RPMI 1640 for 24 and 48 hours in vitro. RESULTS: The activities of LDH and ACP increased in the hTM induced by PPM, and the levels of TNF-? and IL-6 in the hTM induced by PPM increased markedly too. And the induced expression effect of TNF-? and IL-6 is associated with the concentration of PPM, and time for PPM inducing. CONCLUSION: PPM can induce cytokines secretion in hTM,and activate hTM in vitro.

Objective To quantitatively assess the changes of white matter in 15 patients with motor neuron disease by dif-fusion tensor imaging(DTI)and to explore the possible pathogenesis.Methods Fifteen patients with a diagnosis of motor neu-ron disease and sixteen age- and sex-matched controls without disorders affecting the central nervous system received 3.0T DTI;whole-brain white matter damage was examined using tract-based spatial statistics(TBSS),and fractional anisotropy(FA), mean diffusivity(MD),λ1,λ2,λ3were extracted from the damage region.The data were analyzed by t-test to disclose the differ-ences of white matter between patients and controls.Results As compared with the control group,FA was significantly de-creased(P=0.034)in the left corticospinal tract(CST),while λ2(P=0.124)and λ3(P=0.064)had a trend to increase,but FA(P=0.050)in the right CST had a trend to decrease in the experimental group.However,λ1and MD were not significantly different between the two groups.Conclusion DTI can quantitatively evaluate CST degeneration in patients with motor neuron disease,which may be caused by demyelination.

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intraabdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, Cmax was 11.151 microg/mL at 5 min after the intravenous injection and t1/2 was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.
Animals ; Anti-Bacterial Agents ; Body Weight ; Escherichia coli ; Heart ; Humans ; Injections, Intravenous ; Intraabdominal Infections* ; Kidney ; Kinetics ; Liver ; Lung ; Male ; Pharmacokinetics* ; Plasma ; Rats ; Skin ; Spleen ; Viscera

Pharmaceutical excipients, as an indispensable part of drug preparation, play crucial roles as drug carriers, improving drug release, ensuring drug stability, and enhancing patient compliance. Traditional Chinese Medicine (TCM) boasts a rich developmental history. With the modernization of technology, the deep integration of pharmacy, chemistry, and materials science has provided broader opportunities for innovative research in TCM. Simultaneously, the demand for high-quality excipients has become increasingly critical.This paper aims to review current research and applications of excipients in TCM preparations, including pre-mixed and co-processed excipients, modified excipients, and the unification of drugs and excipients, such as flavoring agents, fillers, penetration enhancers, and delivery systems. A meticulous synthesis and analysis of existing research aims to provide a reference for selecting excipients in TCM preparations, stimulate innovation in excipient development for TCM, and advocate for the development of personalized excipients.

Objective To investigate the relationship between cognitive impairment and sleep parameters in acute ischemic stroke patients with obstructive sleep apnea(OSA).Methods A total of 343 patients with acute ischemic stroke and OSA were selected.The cognitive function was assessed using the simple mental state examination scale(MMSE).Patients were divided into the stroke with OSA and cognitive impairment group(MMSE＜27 points,n=119)and the stroke with OSA without cognitive impairment group(MMSE≥27 points,n=224).General data,TOAST etiological classification and distribution of cerebral infarction lesions were collected.The intelligent sleep monitoring system was used to calculate apnea hypopnea index(AHI)and evaluate OSA.Objective sleep monitoring parameters were collected at night.Sleep monitoring was conducted within 24 h of admission and continuous monitoring for≥3 nights.Continuous monitoring duration≥7 h every night to obtain night sleep structure parameters.Multifactor Logistics regression was used to analyze the relationship between cognitive impairment and sleep parameters in stroke patients with OSA.Results Compared with the stroke with OSA without cognitive impairment group,the proportion of age,diabetes history and HHcy history,the proportion of patients with infarct lesions located in frontal,temporal,parietal,occipital,thalamus,basal ganglia,brainstem and hemioval center increased in the stroke with OSA and cognitive impairment group,and the number of years of education decreased,the number of waking times,the proportion of light sleep and AHI increased,the nighttime sleep efficiency and deep sleep period decreased(P＜0.05).Logistics regression analysis showed that after controlling for years of education,age and other interference factors,nighttime sleep efficiency and AHI were strongly associated with cognitive impairment in acute ischemic stroke patients with OSA(P＜0.05).The increased nighttime sleep efficiency was protective factor for cognitive impairment,and increased AHI was risk factor for cognitive impairment.Conclusion Cognitive impairment in acute ischemic stroke patients with OSA is closely related to sleep parameters,in which the increased sleep efficiency at night is a protective factor for cognitive impairment,and the increased AHI is a risk factor.

Objective:To identify the gene mutations associated with facial cleft-related orbital hypertelorism in 3 pairs of monozygotic twins with different phenotypes (with/without hypertelorism) and to investigate their mechanisms.Methods:From May 2014 to May 2019, 3 pairs of monozygotic twins, 2 males and 4 females, aged 5-18 years, were treated in Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, one with normal orbital distance and widening of orbital distance was caused by facial fissure. Among the twins, there was 1 case of orbital hypertelorism and the other case of without orbital hypertelorism, and the hypertelorism was caused by facial cleft. To screen for mutations in hypertelorism, whole genome sequencing was performed on 3 pairs of twins. The Sanger method was used to sequence the exons of 33 patients with facial fissure associated hypertelorism and 50 healthy individuals in the same period to identify the genes selected by the whole genome sequencing. The periosteal tissues were obtained from patients and healthy people during plastic surgery. The cells were cultured, the activity of alkaline phosphatase was measured, and the osteogenic differentiation was identified by alizarin red staining, real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expression of signal transduction pathways in periosteal cells.Results:Whole genome sequencing analysis showed that in all three sets of twins, a new synonymous mutation (c.1479G>A, p. Q493Q) was found in the MAML3. In Sanger exon sequencing, 17(51.5%) of 33 patients with hypertelorism carried the mutation, while no mutation was detected in 50 normal controls. The result of periosteum-derived cytology showed that the expression of MAML3 mRNA and protein in the patient-derived cells was lower than that in the healthy-derived cells. Three, 7, 14 days after osteoinduction, the ALP activity in the cells from the patients was higher than that from the healthy subjects (8.540±1.450, 20.740±2.514, 24.090±3.213 vs. 5.268±0.482, 11.680±1.527, 13.200±0.592; all P<0.05). Fourteen days after osteoinduction, the result of alizarin red staining showed that there were more erythema formation in the cells from the patients than those from the healthy subjects, these result suggest that MAML3 mutation may lead to over-differentiation of human periosteal-derived cells. The mRNA and protein expression levels of hes1 and hes5 downstream of the Notch signal pathway were down-regulated in the periosteal cells of the patients, while Wnt3a and β-catenin mRNA and protein expression levels were up-regulated in the Wnt signal pathway. Conclusions:The MAML3 gene (c.1479G>A, p. Q493Q) mutation is one of the causative genes of facial cleft-related hypertelorism. Notch and Wnt/β-catenin signaling pathway play an important role in the pathogenesis of hypertelorism.