OBJECTIVE To mine adverse drug event （ADE） signals of lacosamide， and to provide references for clinically safe drug use. METHODS ADE data for lacosamide reported to the United States FDA adverse event reporting system from January 1， 2009， to December 31， 2022， were collected. Data mining was conducted using the reporting odds ratio method and Bayesian confidence propagation neural network method. Classification statistics were performed using the system organ class （SOC） and preferred terms （PT） from ADE terminology set of Medical Dictionary for Regulatory Activities （Version 25.0）. RESULTS A total of 21 360 lacosamide ADE reports were received， identifying 203 ADE signals across 24 SOCs， with 19 signals not included in the drug’s instruction. The top five PTs ranked by occurrence frequency were medication overdose， technical errors during device use， product use issues， intentional product misuse， and therapy discontinuation. The top five PTs ranked by signal strength were changes in seizure presentation type， congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， brain surgery， and vagus nerve stimulator implantation. ADEs not recorded in the drug instruction included congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， mitochondrial DNA mutation， dissociative identity disorder， and congenital auricular anomaly. CONCLUSIONS For lacosamide-induced ADEs that occur frequently and are already listed in the drug’s instructions， such as bradycardia and atrioventricular block， the clinical application should be careful and attentive， adjusting the dosage timely according to the patient’s condition to avoid severe ADEs. Newly discovered suspect ADEs， such as congenital hypoplasia of depressor anguli oris muscle， mitochondrial DNA mutation， overmature infant， dissociative identity disorder， pigmenturia， behavioral disorders， and dissociative disorders， should be vigilantly recognized to ensure the safety of drug use.

Objective:To explore the feasibility and superiority of applying digital orthopedic technology of virtual human reconstruction and 3D printing to CBL teaching of kyphosis for clinical postgraduates.Methods:Thirty postgraduates of professional degree participated in the standardized training of resident doctors in our department were randomized into the experimental group (New CBL teaching mode group) and the control group (traditional teaching mode group) with 15 students in each group, and the two groups were taught differently (the teaching content was two typical cases of kyphosis). Among them, the experimental group adopted the new CBL teaching mode, and successively conducted small class theory teaching, model explanation, group discussion, preoperative design, surgery observation and specific questions and answers, etc. The control group only used the traditional method to teach theory in a large class. The teaching effect of the two groups was evaluated in t test by SPSS 25.0.Results:For the teaching of patients with ankylosing spondylitis and kyphosis, scores of the satisfaction with class interest, mastery of theoretical knowledge and understanding of operation plan in the experimental group were (9.4±0.2), (91.1±3.8), and (91.5±3.5) respectively, and those in the control group were (8.2±0.4), (82.1±3.5) and (83.1±4.7) respectively, with statistical significance ( P<0.05). Conclusion:In the teaching of kyphosis, the CBL teaching mode based on digital orthopedic technology is superior to the traditional teaching mode, which is conducive to improving clinical skills for students.

Objective:To connect with the measurement data of asbestos dust fiber concentration in foreign countries, improve the accuracy of asbestos fiber detection in China, and understand the dust exposure in the working environment of asbestos and man-made mineral fiber production and processing sites in Zhejiang Province. The fiber count concentrations of working environment in glass fiber, ceramic fiber and asbestos processing plants were measured and compared.Methods:The dust concentration in the working environment of two glass fiber factories, one ceramic fiber factory and eight asbestos products processing factories was measured. The total dust mass concentration was measured according to GBZ/T 192.1-2007, and the fiber count concentration was measured by phase contrast microscope. Kruskal Wallis was used to test and compare the dust concentration in the working environment of each post. The correlation between asbestos mass concentration and fiber count concentration was analyzed by Spearman correlation.Results:Under the phase contrast microscope, there were many short and fine asbestos fibers in the field of vision, and there were many impurities around. The average dust concentration of asbestos processing plant was 3.2 f/ml, and the dust concentration of cotton ginning was the highest (6.68 f/ml) . There was a significantly positive correlation between asbestos fiber count concentration and mass concentration ( r=0.535, P=0.033) . The average fiber count concentration of glass fiber factory was 0.001 f/ml, and the highest was 0.005 f/ml. The average fiber count concentration of ceramic fiber factory was 0.001 f/ml, and the highest was 0.006 f/ml. Conclusion:The fiber count concentration in the working environment of asbestos factory in Zhejiang Province is obviously over the standard, which is one of the important reasons for the high incidence of mesothelioma in this area. Short and small asbestos fibers are easy to be ignored when counting. It is necessary to improve the actual operation process of fiber counting to form a laboratory standard in China.

Objective:To connect with the measurement data of asbestos dust fiber concentration in foreign countries, improve the accuracy of asbestos fiber detection in China, and understand the dust exposure in the working environment of asbestos and man-made mineral fiber production and processing sites in Zhejiang Province. The fiber count concentrations of working environment in glass fiber, ceramic fiber and asbestos processing plants were measured and compared.Methods:The dust concentration in the working environment of two glass fiber factories, one ceramic fiber factory and eight asbestos products processing factories was measured. The total dust mass concentration was measured according to GBZ/T 192.1-2007, and the fiber count concentration was measured by phase contrast microscope. Kruskal Wallis was used to test and compare the dust concentration in the working environment of each post. The correlation between asbestos mass concentration and fiber count concentration was analyzed by Spearman correlation.Results:Under the phase contrast microscope, there were many short and fine asbestos fibers in the field of vision, and there were many impurities around. The average dust concentration of asbestos processing plant was 3.2 f/ml, and the dust concentration of cotton ginning was the highest (6.68 f/ml) . There was a significantly positive correlation between asbestos fiber count concentration and mass concentration ( r=0.535, P=0.033) . The average fiber count concentration of glass fiber factory was 0.001 f/ml, and the highest was 0.005 f/ml. The average fiber count concentration of ceramic fiber factory was 0.001 f/ml, and the highest was 0.006 f/ml. Conclusion:The fiber count concentration in the working environment of asbestos factory in Zhejiang Province is obviously over the standard, which is one of the important reasons for the high incidence of mesothelioma in this area. Short and small asbestos fibers are easy to be ignored when counting. It is necessary to improve the actual operation process of fiber counting to form a laboratory standard in China.

Objective To explore the effects of early functional exercise on the patients with shoulder-hand syndrome after acute stroke. Methods Totally 60 patients with shoulder-hand syndrome after acute stroke who were admitted in Zhejiang Hospital between January 2015 and January 2017 were prospectively selected and randomly divided into an observation group (n=30) and a control group (n=30). Patients in the observation group performed early functional exercise, while patients in the control group received only routine nursing. The clinical effect was compared between the patients in the two groups. Results There was no statistically significant difference in the scores for the swelling of the limb, the range of movement of metacarpophalangeal joints and the simple upper limb function before the intervention (P>0.05). After two weeks and four weeks of intervention, the swelling of the limb in the patients in the observation group was lower than that of the patients in the control group (P< 0.05). After four weeks of intervention, the scores for the range of movement of metacarpophalangeal joints in the patients in the observation group were higher than those of the patients in the control group (P<0.05). There was no statistically significant difference in the scores of anxiety and depression between the patients in the two groups (P> 0.05). After four weeks of intervention, the patients in the observation group showed lower scores of anxiety and depression than the patients in the control group (P<0.05). Conclusions Early functional exercise helps to improve the function of limbs, lower the level of anxiety and depression, and improve the quality of life in patients with shoulder-hand syndrome after acute stroke.

Objective To investigate the effects of matrine on proliferation and apoptosis of human rhabdomyosarcoma(RMS) RD cells line in vitro,to study the regulatory mechanism of Wnt/β-catenin pathway-influenced apoptosis of RD cells line by detecting the expressions of β-catenin protein,Bcl-2 protein and caspase-3 protein,and to explore Wnt/β-catenin mechanism during the process of RMS.Methods The human RMS RD cells line was treated with matrine of different concentrations (0.5,1.0,1.5,2.0 g/L)for 48 hours respectively,and the proliferation inhibition rates of different concentrations of matrine on RD cells were detected by methyl thiazolyl tetrazolium assay,while the apoptosis rates by flow cytometry (FCM) and the expressions of β-catenin,Bcl-2 and caspase-3 by Western blot.Results The proliferation inhibition rates between control group and different concentrations of matrine groups were(13.70 ±0.25)％,(33.16 ±0.11)％,(42.96 ±0.90)％,(56.26 ±0.79)％ and (67.89 ±0.63)％,respectively.The apoptosis rates were (5.49 ± 0.96) ％,(17.23 ± 5.03) ％,(25.84 ± 4.17) ％,(36.08 ± 3.68) ％and (47.79 ± 4.82) ％,respectively.The highest expression of β-catenin and Bcl-2 proteins and the minimum amount of caspase-3 protein were found in the control group.After intervention of matrine,the expressions of β-catenin and Bcl-2 reduced while the amount of caspase-3 rose significantly,which was concentration-dependent obviously.Differences were found between every concentration of matrine group with control group according to statistics (all P ＜ 0.05).Conclusions Matrine can inhibit proliferation and induce apoptosis of RD cells.Matrine can down-regulate the expression of β-catenin and Bcl-2 proteins in RD cells,while the amount of caspase-3 protein rises.Wnt/β-catenin signal pathway plays an important role in the apoptosis of RD cell induced by matrine,and its downstream proteins Bcl-2 and caspase-3 are also involved in the regulation of this process.

ObjectiveTo explore the role of the lymphocyte subsets in the peripheral blood in diagnosis, treatment and prognosis of hemophagocytic lymphohistiocytosis (HLH) in children.MethodA total of 30 children with HLH were enrolled in this study and treated according to the HLH-2004 diagnostic guidelines. 20 children with HLH entered complete remission (CR) and 10 children with HLH died. Thirty age-matched healthy children were selected as normal controls. T cell subsets in the pe-ripheral blood were measured by lfow cytometry.ResultsCompared with control group, CD3+T and CD8+T cells were signiif-cantly increased, CD4+T and CD3-CDl6+CD56+ NK cells were signiifcantly decreased, and CD4+/CD8+ cell ratio was signiifcantly decreased in 20 CR children and 10 died children with HLH in acute phase (P<0.05). CD19+B cells was not statistically different in 20 CR children and 10 died children with HLH in acute phase from control group (P>0.05). In acute phase, the lymphocyte subsets were not statistically different between 20 CR children and 10 died children (P>0.05). In 20 CR children, the proportion of CD3-CD16+CD56+NK in CR phase was statistically different than that in acute phase (P<0.05).ConclusionsChildren with HLH have obvious changes in peripheral blood lymphocyte subsets and have cellular immunity disorders. Dynamic detection of the changes may help determine the therapeutic effect and prognosis of HLH.

Air Pollutants, Occupational ; toxicity ; Humans ; Occupational Exposure ; adverse effects ; Welding

Objective To investigate the relationship between p53,COX-2,Bax,c-myc genes and colorectal carcinoma complicated with chronic schistosomiasis. Methods One hundred and sixty patients with colorectal carcinoma were selected and divided into two groups;a schistosomiasis group(colorectal carcinoma complicated with chronic schistosomiasis,n=80)and a non-schistosomiasis group(colorectal carcinoma uncomplicated with chronic schistosomiasis,n=80). The tissue microarray tech-niques and immunohistochemistry method were used in all the patients to detect the expressions of p53,COX-2,Bax and c-myc proteins. Results The positive rate and level of p53 protein expression in the schistosomiasis group were lower than those in the non-schistosomiasis group,but there were no significant differences between the two groups(both P>0.05). The COX-2 protein in both groups was positive,but the positive expression level of COX-2 in the schistosomiasis group was higher than that in the non-schistosomiasis group,and there was a significant difference between the two groups(P<0.01). The positive rate and level of Bax protein expression were not significantly different between the two groups(both P>0.05). The positive rate of c-myc expression in the schistosomiasis group was higher than that in the non-schistosomiasis group,with a significant difference(P<0.01),but the positive expression level was lower than that in the non-schistosomiasis group,and there was a significant difference between the two groups(P<0.01). Conclusions Schistosome infection may impact on the deficiency of p53 of human colorectal cancer cells. It may promote the excessive expression of COX-2 protein,which is an indirect carcinogenic factor. The expression of Bax gene has no correlation with schistosome infection. The schistosome chronic infection may cause a persistent low level expression of c-myc gene.

Aquilaria sinensis callus induced by stem tips were used to establish the suspension cell system. The results showed that the most suitable medium for callus induction and subculture is MS + 2.0 mg x L(-1) NAA + 1.0 mg x L(-1) 6-BA. After 12 times of subculture, the energetic and loose callus, which were appropriate for cell suspension culture, were cultured and shook in liquid medium MS + 2.0 mg x L(-1) NAA + 1.0 mg x L(-1) 6-BA + 500.0 mg x L(-1) casein hydrolysate (CH) to establish the suspension cell system. The growth curve of suspension cells showed a "S" type. At the beginning of the culture, cell density increased slowly; during 4 to 6 days, suspension cells reached logarithmic growth period; during 7 to 12 days, suspension cells were in the platform period; but after 12 days, cell density and activity went down obviously. Agarwood sesquiterpenes were not detected in the suspension cells during the growth period, however, they could be detected in MeJA treated suspension cells. In this study, a stable and active growing suspension cell system was established, which was a proper system to study the mechanism of agarwood sesquiterpene formation, and additionally provided a potential way to generate agarwood sesquiterpenes through application of cell culture.