Safety and efficacy of oral Lacosamide as an add-on therapy in Chinese children with partial-onset seizures / 中华实用儿科临床杂志

Objective:To evaluate the long-term safety, tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods:SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially, partial seizures were still poorly controlled and Lacosamide oral solution (syrup) or tablets were added.The minimum initial oral dose was 2 mg/(kg·d), and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded, including 50% responder rate and 75% responder rate.Results:A total of 60 Chinese children with the mean age of 9.18 (4.00-15.40) years were included in this interim analysis, involving 39 males and 21 females.The mean course of epilepsy was 5.04 (0.50-15.20) years.A total of 43 patients (71.7%) still have been treated.One patient (1.7%) has completed the 6-12 months of follow-up, and 14 patients (23.3%) have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was -2.91, with its median percentage as -25.46%, and the proportions of ≥50%, while ≥75% responder rate were 40.0% and 28.3%, respectively.A total of 52 patients (86.7%) had 265 treatment emergent adverse events (TEAE), 11 patients (18.3%) had 19 serious TEAE, 37 patients (61.7%) had 127 drug-related TEAE, and 11 patients (18.3%) had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections (20 cases, 33.3%), followed by drowsiness (16 cases, 26.7%), dizziness (15 cases, 25.0%) and vomiting (13 cases, 21.7%). There were no abnormal changes in the electrocardiographic findings during the treatment.Conclusions:For Chinese patients with partial seizures who are older than the age of 4 years and poorly controlled by other drugs, Lacosamide is effective and well tolerated as an add-on therapy drug.The safety characteristics are consistent with those reported in children and adults.No new safety concerns are identified.

Analysis of monitoring results of coal-burning-borne endemic arsenism in Shaanxi Province from 2015 to 2020 / 中华地方病学杂志

Objective:To learn about the changes of the condition of coal-burning-borne endemic arsenism, the use of improved stoves and the formation of health-related behaviors in Shaanxi Province, and evaluate the effect of prevention and control measures.Methods:From 2015 to 2020, according to the "Implementation Plan for Monitoring Coal-burning-borne Endemic Arsenism in Shaanxi Province", regular field surveys were carried out in 4 natural villages, 2 counties in Ankang City and Hanzhong City, Shaanxi Province, to learn about the basic prevention and control situation in the monitoring village. Using the simple random sampling method, 10 families in each village were selected to investigate the use of stoves and the formation of health-related behaviors, and 5 of these families were selected to collect coal samples for arsenic content determination in accordance with the "Determination of Arsenic in Coal" (GB/T 3058-2008). According to the "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015), the condition of the people exposed to high arsenic coal in the monitoring village was investigated. Urine samples of 30 adult patients (half males and half females) with arsenic poisoning were collected, the content of arsenic in urine was determined by the "Urine-Determination of Arsenic-Silver Diethyldithiocarbamate-Triethanolamine-Spectrophotometric Method" (WS/T 28-1996).Results:A total of 240 households were monitored in the past 6 years, and the quality conformance and correct utilization rates of improved stoves in the households monitored in the disease areas remained at 100.00% in 2018 - 2020. The utilization rate of clean energy increased from 75.00% (30/40) in 2015 to 100.00% (40/40) in 2018 - 2020 (χ 2trend = 25.5, P < 0.001). The 73.75% (177/240) of households using a variety of clean energy. From 2018 to 2020, the correct drying, storage and pre-processing washing rates of corn and pepper continued to reach 100.00% (40/40). The arsenic content of coal ( n = 120) in the disease areas was (118.09 ± 57.91) mg/kg, ranging from 16.70 to 280.94 mg/kg. The detection rate of arsenic poisoning decreased from 6.34% (231/3 646) in 2015 to 2.90% (109/3 754) in 2020 (χ 2trend = 121.8, P < 0.001), and no skin cancer or Bowen's disease was detected. The geometric mean of arsenic content in urine ( n = 720) was 0.038 1 mg/L, ranging from 0.000 5 to 0.312 9 mg/L. Conclusions:The condition of coal-burning-borne endemic arsenism areas in Shaanxi Province has reached the national elimination standard. The quality and correct utilization rate of improved stoves and the rate of using clean energy have increased. The healthy-related behaviors the people in the endemic areas have been basically formed. The prevention and control work has achieved good results.

The radiosensitization effect of STING agonist on cutaneous melanoma cells / 中华放射医学与防护杂志

Objective:To investigate the radiosensitizing effect and underlying mechanism of STING agonist (c-di-AMP) on cutaneous melanoma cells.Methods:Human cutaneous melanoma cells (A375) were divided into four groups: the control group, 10 μmol/L c-di-AMP group, X-ray irradiation group and X-ray irradiation combined with c-di-AMP group. The radiosensitizing effect of c-di-AMP on A375 cells was detected by CCK-8-based viability assay, lactate dehydrogenase (LDH) release assay, flow cytometry-based apoptosis assay, and colony formation assay. Western blot analysis was used to determine the expressions of cell death-related proteins.Results:In combination with 10 Gy X-ray irradiation, 10 μmol/L c-di-AMP showed significant radiosensitization effect in A375 cells, which was evidenced by decreased cell activity ( t=5.11, P<0.05), increased cytotoxicity ( t=10.15, P<0.05) and cell apoptosis ( t=4.41, P<0.05) and reduced clone viability( t=6.30, 3.55, 5.45, 3.55, P<0.05). The calculated radiosensitization ratio of c-di-AMP to A375 cells was 1.88. Moreover, 10 μmol/L c-di-AMP further increased the expressions of cell death-related proteins induced by radiation in A375 cells. Conclusions:The STING agonist c-di-AMP can be used as a radiosensitizer for cutaneous melanoma, which may provide a novel strategy for radiotherapy.

The value of dual-layer spectral CT in assessment of solid lung adenocarcinoma based on 2011 and 2020 pathological grading system / 中华放射学杂志

Objective:To explore the value of spectral CT in the preoperative evaluation of solid lung adenocarcinoma with different pathological grades based on the 2011 and 2020 version of the pathological grading system.Methods:A total of 76 cases of solid lung adenocarcinoma confirmed by surgery in Renji Hospital, School of Medicine, Shanghai Jiao Tong University, from January 2019 to September 2021 were analyzed retrospectively. All cases were divided into groups according to the grading system for invasive adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) in 2011 and 2020 (G low group included G1 and G2 adenocarcinoma, G high group included G3 adenocarcinoma). The tumors with stage Ⅰ and Ⅱ were non-advanced and the tumors with stage Ⅲ and Ⅳ were advanced. The clinical manifestations (gender, age, smoking history and stage), routine CT parameters (tumor size, morphological characteristics, plain CT value and enhancement degree) and spectral parameters [iodine concentration, effective atomic number, enhanced monochromatic CT attenuation values of 40-200 keV (CT 40 keV-CT 200 keV), and the slope of spectral curve (k value)] were compared between G low group and G high group using independent sample t-test or Mann-Whitney U test. And the efficacy of each parameter for indicating G high adenocarcinoma was analyzed using receiver operating characteristic curve analysis and area under the curve (AUC), and the Z test was used to compare the AUC. Results:Seventy-six cases were included (59 cases of G low group and 17 cases of G high group in 2011 version; 46 cases of G low group and 30 cases of G high group in 2020 version). Among the 76 cases, 62 cases were non-advanced stage (50 cases of G low group and 12 cases of G high group in 2011 version; 37 cases of G low group and 25 cases of G high group in 2020 version) and 14 cases were advanced stage (9 cases of G low group and 5 cases in G high group in both 2011 and 2020 version). Among the non-advanced adenocarcinomas, the CT parameters of enhancement degree, k value and CT 40 keV-CT 60 keV in arterial phase and enhancement degree, k value and CT 40 keV-CT 70 keV in venous phase of G high group in 2011 grading system were significantly lower than those of G low group ( P<0.05), while other parameters were similar between G low and G high group in 2011 grading system ( P>0.05); and the CT parameters of CT 60 keV in arterial phase and CT 50 keV-CT 70 keV in venous phase of G high group in 2020 grading system were significantly lower than those of G low group ( P<0.05). Among the advanced adenocarcinomas, all of the clinical and CT parameters were similar between G low and G high group in both 2020 and 2011 grading systems ( P>0.05). For the non-advanced adenocarcinomas, there was medium to good efficacy of the CT parameters of enhancement degree, k value and CT 40 keV-CT 60 keV in arterial phase and enhancement degree, k value and CT 40 keV-CT 70 keV in venous phase for diagnosing 2011 grading system G high adenocarcinoma (AUC=0.700-0.853), with CT 50 keV in venous phase as the best; while the diagnosis efficacy of CT parameters of CT 60 keV in arterial phase and CT 50 keV-CT 70 keV in venous phase was poor for 2020 grading system G high adenocarcinoma (AUC=0.652-0.688), with CT 60 keV in venous phase as the best. After combining smoking history and CT 60 keV in venous phase, the diagnosis efficacy for 2020 grading system G high adenocarcinoma was slightly improved (AUC=0.772), but the difference had no significance ( Z=0.93, P=0.176). Conclusion:The spectral parameters are useful for distinguishing the pathological grades of solid lung adenocarcinoma. And the detecting efficacy for G high adenocarcinoma of IASLC 2011 version is slightly better than that of 2020 version.

Correlation between the prevalence of dental fluorosis and dietary nutrient intake in children / 公共卫生与预防医学

Objective To investigate the correlation between the prevalence of dental fluorosis in children and the intake of dietary nutrients. Methods A total of 81 children aged 8-12 (34 males and 47 females) with fluorosis were randomly selected in the districts of Daxu, Fuping, and Fuyang in Shaanxi Province where the drinking water had been changed for more than 5 years. The diagnosis of dental fluorosis was carried out using Dean's method. According to the 1:1 case-control study method, 81 children aged 8-12 (34 males and 47 females) without dental fluorosis were selected as a control group. A “double meal method“ was employed for dietary investigation for 3 consecutive days. The differences in dietary nutrient intake between the two groups of children were analyzed and compared. Results There was no significant difference between the two groups (P>0.05). Compared with the control group, the difference in the dietary intake of vitamin C, vitamin E, calcium, magnesium, iron, zinc, copper, phosphorus, and selenium in the fluorosis group was not statistically significant (P>0.05). The logistic regression analysis of the prevalence of dental fluorosis in children showed that the dietary nutrient magnesium was associated with the onset of dental fluorosis. Conclusion Within a certain range, dietary magnesium is a protective factor for children with dental fluorosis. It is suggested that school-age children in areas with excessive water fluoride should be supplemented with sufficient magnesium in their diets.

Effect of prevention and control measures on drinking-water-borne endemic arsenic poisoning in Shaanxi Province / 中华地方病学杂志

Objective:To investigate the arsenic content in internal and external environment of the people in drinking-water-borne endemic arsenic poisoning areas in Shaanxi Province, the status quo of the disease and the management and services of the existing patients, so as to provide a theoretical basis for evaluating the effect of prevention and control measures on drinking-water-borne endemic arsenic poisoning.Methods:From 2019 to 2020, in accordance with the requirements of the "Notice of Shaanxi Provincial Health Commission on Issuance of Monitoring Plans for Key Endemic Diseases such as Kashin-Beck Disease" and "Monitoring Plans for Drinking Water Arsenic Poisoning in Shaanxi Province", investigation was carried out in all villages of drinking-water-borne endemic arsenic poisoning in Mianxian County of Hanzhong City, Shanyang County and Zhen'an County of Shangluo City to understand the operation of water improvement project. One terminal water sample was collected to determine the content of arsenic in water, and permanent population of the whole village who are and/or had been exposed to excessive arsenic water in the past were examined for arsenic poisoning and the disease condition was determined according to the standard of "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015). Five villages were randomly selected, and 50 people were selected from each village. Real-time urine sample was collected to determine the content of urinary arsenic. At the same time, management and services of the existing arsenic poisoning patients was investigated.Results:A total of 13 villages were investigated, all of which had been improved in water quality, and all 13 water improvement projects were operating normally, with arsenic content < 0.01 mg/L. A total of 12 577 people were examined, and 417 cases of arsenic poisoning were detected, with a detection rate of 3.32%. No new arsenic poisoning case and arsenic-related skin cancer case had been detected. A total of 260 urine samples were detected, and the geometric mean value of urinary arsenic (< 0.001 mg/L) was lower than the safety guideline value of human urinary arsenic (0.032 mg/L). The existing arsenic poisoning patients (417 cases) were included in health management and contracted services.Conclusions:Shaanxi Province has reached the elimination standard of drinking-water-borne endemic arsenic poisoning. In the future, more attention should be paid to the management of water improvement project, as well as to strengthen health promotion and management services for existing patients to consolidate the effects of prevention and control.

Value of dual-layer spectral detector CT in differentiating the diagnosis of lung cancer and inflammatory nodules / 中华放射学杂志

Objective:To explore the value of dual-layer spectral detector CT in differentiating the diagnosis of lung cancer and inflammatory nodules.Methods:A total of 92 patients undergoing enhanced chest scan from March 2019 to September 2020 at Renji Hospital, School of Medicine, Shanghai Jiaotong University, were retrospectively enrolled in the study. The conventional CT parameters, spectral CT parameters were measured and the nodules′ morphological characteristics were analyzed. Later the factors with statistical significance were identified as independent variables in a logistic regression model to establish models for predicting malignant nodules. ROC curve was used to assess the diagnostic performance for the conventional CT model, spectral CT parameters and combined model, respectively. Differences in the area under the ROC curve (AUC) were analyzed by the DeLong test.Results:Lobulated sign (42 and 8, respectively, χ2=10.779, P=0.001), short burr sign (41 and 7, respectively, χ2=11.911, P=0.001), pleural indentation sign (45 and 9 respectively, χ2=11.705, P=0.001), vascular convergence sign (35 and 8, respectively, χ2=5.337, P=0.021) and the venous phase iodine concentrations (IC) value [(2.1±0.5) mg/ml, (2.3±0.5) mg/ml, t=-2.464, P=0.016], normalized iodine concentrations (NIC) value (0.40±0.06, 0.45±0.08, t=-6.943, P<0.001), and Z-effective (Z eff) values (8.38±0.21, 8.49±0.19, t=-2.122, P=0.037) were significantly different between the lung cancer group and the inflammatory group, while other CT signs and CT indicators were not significantly different between the lung cancer group and the inflammatory group ( P>0.05). The conventional CT model was established with lobulated sign, short burr sign, pleural indentation sign, vascular convergence sign, and the AUC for differential diagnosis of lung cancer and inflammatory nodules was 0.827. The spectral CT parameter model was established with venous phase IC, venous phase NIC, and venous phase Z eff value, and the AUC for differential diagnosis of lung cancer and inflammatory nodules was 0.899. The conventional CT model combined spectral CT parameter model was established with the significant factors in the univariate analysis, and the AUC for differential diagnosis of lung cancer and inflammatory nodules was 0.925. The AUC of the combined model showed no significant difference from that of the spectral CT parameter model ( Z=1.794, P=0.073). However, AUC of the combined model was significantly higher than that of evaluation based on conventional CT alone ( Z=2.156, P=0.031). Conclusion:Spectral CT parameters combined with conventional CT signs can improve the differential diagnosis efficiency between lung cancer and inflammatory nodules.

Benchmark dose of the children's total fluoride intake / 中华地方病学杂志

Objective:By exploring the source of children's total fluoride intake and the relationship between children's total fluoride intake and dental fluorosis prevalence, to calculate the benchmark dose (BMD) of children's total fluoride intake and its 95% confidence lower limit (BMDL), and to provide the basis for revision of "Total Fluoride Intake for Inhabitants" (WS/T 87-2016).Methods:The villages that had water improvement for 5 years and more in 6 provinces of Jiangsu, Shandong, Hebei, Anhui, Henan and Shaanxi were selected as survey sites in April 2014. The water fluoride content of these villages was 0.3 - 3.0 mg/L, tap water samples from the centralized water supply were collected, and fluoride content was detected by ion selective electrode method. Children aged 8 to 12 years were selected, children's dental fluorosis was checked by Dean's method. Children's dietary and drinking water volume were surveyed by duplicate portion study (measurement for 3 d), and dietary fluoride content was detected according to the "Method for Determination of Fluorine in Foods". The mean and standard deviation of drinking water fluoride intake, dietary fluoride intake, and total fluoride intake were measured. According to the dose-response relationship between children's total fluoride intake and the detection rate of dental fluorosis, BMD and BMDL were calculated, and the reference dose (RfD) was calculated based on BMDL.Results:The mean of water fluoride of all 29 villages was 1.26 mg/L (from 0.41 to 2.85 mg/L). Totally 3 043 children aged 8 to 12 years were checked, and the detection rate of dental fluorosis was 30.2% (919/3 034). The lowest detection rate of dental fluorosis was 2.0% (2/100) and the highest was 71.4% (30/42) in the 29 villages. The children's dietary and drinking water volume of 769 person-time aged 8 to 12 years were surveyed, the children's daily drinking water fluoride intake, dietary fluoride intake, and total fluoride intake were (0.83 ± 0.66), (1.13 ± 0.61) and (1.96 ± 0.89) mg/d, respectively. The BMD of children's daily total fluoride intake was 2.43 mg, the BMDL was 2.21 mg, and the RfD was 2.21 mg.Conclusion:The BMD of 8 to 12 years old children's daily total fluoride intake is the same as the allowable limit (2.4 mg) of the national standard "Total Fluoride Intake for Inhabitants" (WS/T 87-2016).

Investigation on the correlation between water fluorine content and dental fluorosis and caries of children in Shaanxi Province / 中华地方病学杂志

Objective:To investigate the relationship between different fluorine concentrations in drinking water and dental fluorosis and caries of children.Methods:In 2014-2019, 5 cities and 6 counties (districts) were selected, which were Dali and Heyang counties of Weinan City, Liquan County of Xianyang City, Fugu County of Yulin City, Chencang District of Baoji City, and Yanliang District of Xi'an City, villages of different water fluorine contents were selected, 3 tap water samples were collected from each village to detect the water fluoride content. The prevalence of dental fluorosis and caries in children aged 8 to 12 years old in villages was investigated, and children's urinary fluorine level was determined.Results:Totally 48 water samples and 868 urine samples were tested, and the water fluorine content was from 0.23 to 3.70 mg/L, and the urinary fluorine mean was 1.47 mg/L; 1 021 children aged 8-12 years old were examined, 372 were diagnosed with dental fluorosis, the detection rate was 36.43%; 198 with caries, the detection rate was 19.39%. The detection rate of caries in children decreased and then increased with the increase of water fluorine ( F=14.470, P < 0.05), and the detection rate of caries was the lowest when the water fluorine was 1.2-< 2.0 mg/L. The detection rate of dental fluorosis in children increased with the increase of water fluorine ( F=52.215, P < 0.05), when the water fluoride was 1.0-< 1.2 mg/L, the detection rate of children's dental fluorosis was 31.90% (37/116), which was basically within the national control line (30%). Conclusion:The content of water fluoride in 1.0-< 1.2 mg/L, can not only reduce the detection rate of caries, but also control the prevalence of dental fluorosis.

Clinical analysis of hypersensitivity reactions to oxaliplatin / 中国肿瘤临床

Objective: To analyze the clinical characteristics of allergic reactions in patients with colorectal cancer after routine premed-ication with dexamethasone (5 mg) before chemotherapy with an oxaliplatin-containing regimen and to provide a reference for reduc-ing the risk of oxaliplatin allergy. Methods: Retrospective analysis of 242 patients with colorectal cancer who received chemotherapy with an oxaliplatin-containing regimen at the Changzhou Cancer Hospital of Soochow University from January 2014 to October 2017 was performed, and the incidence of allergic reactions was calculated. The associations between multiple factors and allergic reactions were then assessed using univariate analysis. The independent factors of allergic reactions were assessed using multivariate Logistic analysis, and the treatment outcome of oxaliplatin rechallenge in allergic patients was discussed. Results: A total of 242 patients were studied. They received routine premedication with dexamethasone (5 mg) before chemotherapy with an oxaliplatin-containing regi-men. Twelve (4.9%) patients had type I allergic reactions, with a median onset time of 6 (5.5-10.5) cycles and a median cumulative dose of 895 (716.5-1 075.0) mg. Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (P=0.04). Rechallenging patients with prophylactic agents was successful in 1 (33.3%) of 3 patients who completed their treatment. Conclusions: Routine low-dose dexamethasone premedication before oxaliplatin administration is safe and exhibited a lower inci-dence of hypersensitivity reactions than that reported in literature. An oxaliplatin-free interval may increase the risk of hypersensitivity reactions. Caution should be exercised while rechallenging allergic patients with oxaliplatin.

Clinical follow-up observation of 84 cases of implant-retained/supported prostheses in edentulous patients / 中华口腔医学杂志

Objectives@#To evaluate the long-term clinical results and patient satisfaction of implant-retained/supported prostheses in edentulous patient based on retrospectively summary of the clinical data of implant-retained/supported prostheses patients.@*Methods@#Edentulous patients who received implant denture treatment between 01/2005 and 12/2016 was included in this study. Soft tissue health, clinical examination, X-ray observation, patient satisfaction with implant-retained/supported prostheses were evaluated.@*Results@#A total of 400 implants in 84 cases (96 jaws), 35 fixed bridges and 61 overdentures. The follow-up time was (34.3±25.5) months. The 3- and 5-year implant cumulative survival rate of implant-supported overdenture was 95.0% and 92.1%, and the 3- and 5- year survival rate of implant-supported fixed denture was both 99.9%. The prevalence of peri-implantitis was 2.8% (11/400). A total of 44% (27/61) of the overdenture and 23%(8/35) of the fixed denture were repaired due to the complications of prosthesis. The mean repair frequency was (1.4±1.2) in overdenture and (1.3±0.9) in fixed denture (t=0.490, P=0.600). The average probing depth around implant recorded in the overdenture group [(2.2±1.1) mm] was significantly greater than that in the fixed denture group [(1.4±1.2) mm] (t=3.300, P=0.002). Patient satisfaction with an average of (6.5±4.9) in implant-support overdenture group was significantly higher than that in implant-support fixed denture group (3.2±2.8) (t=3.218, P=0.006).@*Conclusions@#The complication rate of the prosthesis was high in edentulous patients with implant-retained/supported prostheses. Besides, the patients with implant supported denture expressed more satisfaction with their prostheses. And there was a relatively high implant cumulative survival rate of implant-retained/supported prostheses in edentulous patient.

Study on pathogenesis and traditional Chinese medicine syndrome differentiation of acute lung injury / 中国中西医结合急救杂志

Acute lung injury (ALI) and its evoked acute respiratory distress syndrome (ARDS) are the main causes of acute respiratory failure (ARF) in many clinical severe diseases, so that ALI is one of the clinical serious respiratory diseases. The mortality of ALI is persisting at high level without any lowering. And its basic pathological manifestations often show injury of pulmonary capillary membrane caused by uncontrolled inflammation, pulmonary edema and formation of transparent membrane. In this article, from the point of view of inflammation, oxidation stress, cell apoptosis, autophagy, etc to comprehensively summarize the pathogenesis of ALI, explaining the relationships between the occurrence of ALI and the uncontrolled inflammation, cytokines release, the unbalance of oxidation and anti-oxidation system, and different inducing factors leading to cellular autophagy. Moreover, the general research situation of traditional Chinese medicine and Chinese herbal compound prescription for treatment of ALI was summarized. According to the TCM theory of "lung and the large intestine being interior-exteriorly related", the TCM method of Xuanfeitongfu method was proposed to be used for prevention and treatment of ALI, and from the point of view of inflammatory reaction regulation and autophagy pathway, the theoretical connotation was revealed, aiming to provide a direction for basic research and development of new traditional Chinese medicine for treatment of ALI.

Mechanism and effects of NMDA receptor NR1 subunit on chronic constriction injury-induced neuropathic pain in a rat model / 中国医师杂志

Objective To investigate the effects of intrathecal injection (IT) of agonist and antagonist of N-methyl-D-aspartate receptor subunit 1 (NMDA NR1) on pain threshold and spinal levels of glutamate and glutamate transporter-1 (GLT-1) in rat model of chronic constriction injury (CCI) induced neuropathic pain.Methods Sprague-Dawley (SD) rats were randomly divided into 4 groups (Sham,CCI,NM-DA,and Humanin).The CCI model was established by right sciatic nerve constriction.The thermal and mechanical thresholds were assessed by paw withdrawal latency (PWL) to radiant heat and yon Frey filaments at 1,3,5,7,10 and 14 days as well as behavior after CCI.The NMDA and Humanin groups were administered intrathecally for 3 days before surgery.Spinal expression of GLT-1 assessed by Weston blotting and levels of glutamate were measured by enzyme-linked immunosorbent assay (ELISA).Results Compared to Sham group,the rats in CCI group gradually appeared the symptoms of toe close together,foot valgus and repeated licking to the operative side of the hind legs after surgery,and the paw withdrawal threshold (PWT),and PWL were greatly decreased,reaching the lowest level on the 7th day.Meanwhile,the glutamate content was increased,and the GLT-1 expression was decreased in spinal cord (P ＜ 0.05).Compared to CCI group,the rats in NMDA group were observed with further decrease in PWT,PWL and GLT-1 expressions at all observed timepoints (P ＜ 0.05),but increase in glutamate content in spine cord (P ＜0.05).Compared to CCI group,the rats in Humanin group were observed with increase in PWT,PWL and GLT-1 expressions at all observed timepoint (P ＜ 0.05),but decrease in glutamate content in spine cord (P ＜ 0.05).Conclusions NMDA receptor NR1 subunit participated in regulating neuropathic pain,inhibiting NMDA receptor NR1 subunit can alleviate neuropathic pain by down-regulating of glutamate and GLT-1.

Correlation between hair and urinary arsenic and selenium level and seriousness of patients with arseniasis in coal-burning-borne arsenic areas / 中华地方病学杂志

Objective To investigate the relationship between levels of arsenic and selenium in hair and urine of patients with arsenic poisoning caused by coal-burning.Methods Based on the Standard of Diagnosis for Endemic Arsenism (WS/T 211-2001),about fifty arsenism or suspicious patients over 40 years old were separately selected from Haoping Town and Shuang'an Town of Ziyang County,and the high-arsenic stone coal of Haoping Town was consumed in these two towns,all patients were divided into suspicious,light,moderate,and severe groups.Five coal samples were collected from homes of patients with arsenic poisoning,which were crushed to pieces and sufficiently mixed,0.5 kg of the crushed coal was collected by quartering method to determine arsenic and selenium content;at the same time,5 water samples were collected in homes of patients with arsenic poisoning to determine arsenic and selenium content;in each investigation site,5 ploughs were selected according to the five directions as east,west,south,north and centre,to collect 15-30 cm soil of plough layer,after blending with four points method of shrinkage,1.0 kg was collected to determine arsenic and selenium content in the soil;the urine of all patients instantly and 0.5 g hair sample within 20 mm from the scalp on occiput were collected to determine arsenic and selenium content.Dual channel atomic fluorescence spectrophotometer was used to measure the arsenic and selenium content in the coal,water,soil,urine and hair samples.The contents of arsenic and selenium in coal,water and soil were expressed as （x） ± s;the contents of arsenic and selenium in urine and hair were expressed as medium (M) and quartile range (QR).Results The patients with arseniasis in moderate and severe groups from Shuang'an Town accounted for 9.8％ (5/51) of the total number of patients;the patients in moderate and severe groups from Haoping Town accounted for 39.2％ (20/51).Compared between the two towns of the proportion of arsenic poisoning clinical index,the difference was statistically significant (x2 =31.224,P ＜ 0.01).Compared between Haoping Town and Shuang'an Town,the arsenic contents of soil [(150.71 ± 127.10),(71.10 ± 22.75) mg/kg],water [(0.004 1 ± 0.000 2),(0.006 3 ± 0.000 4) mg/L],urine [0.025 2 (0.023 2),0.026 7 (0.025 6) mg/L] and hair [2.54 (3.52),2.81 (5.98) mg/kg] were not significantly different (Z =-0.913,-1.776,-0.079,-0.544,all P ＞ 0.05).The selenium contents of soil [(5.93 ± 5.76) mg/kg],water [(0.036 9 ± 0.001 8) mg/L],urine [0.056 3 (0.152 2) mg/L] and hair [3.65 (5.43) mg/kg] in Shuang'an Town were higher than those of Haoping Town [(2.41 ± 1.03) mg/kg,(0.006 1 ± 0.000 6) mg/L,0.015 6 (0.013 4) mg/L and 1.52 (2.05) mg/kg],the differences were statistically significant (Z =-2.619,-2.611,-4.765,-2.485,all P ＜ 0.01).There was a positive correlation between hair arsenic and arsenic in clinical grading (r =0.874,P ＜ 0.01);there was a negative correlation between hair selenium and arsenic in clinical grading (r =-0.400,P ＜ 0.01).Conclusions High selenium environment affects the severity of patients with arsenic poisoning,indicating that selenium may promote arsenic metabolism and reduce arsenic accumulation in vivo.Selenium may have an antagonist effect on arsenic.

Mechanism and Effects of Cannabinoid Receptor 1 on Sciatic Nerve Ligation-induced Neuropathic Pain in Rat Model / 中国医科大学学报

Objective To observe the effects of intrathecal injection(IT)of agonist and antagonist of cannabinoid receptor 1 on pain threshold in rat model of sciatic nerve ligation(SNL)induced neuropathic pain,and investigate the role and mechanism of CB1 in neuropathic pain. Methods Male Sprague-Dawley rats were randomly divided into 4 groups:sham group( intrathecal normal saline,IT DMSO),SNL group(SNL+IT 30μL DMSO),AM841 group(SNL+IT 5μg AM841,dissolved in 30μL of DMSO)and AM281 group(SNL+IT 5μg AM281,dissolved in 30μL of DMSO). IT was given 3 days before surgery. Sham group only had sciatic nerve exposure but without ligation. SNL model in the other three groups were established by right sciatic nerve ligation. The thermal and mechanical thresholds were assessed by paw withdrawal latency(PWL)to radiant heat and von Frey filaments at 1,3,5,7,10 and 14 days as well as behavior after SNL. Spinal expressions of CB1 were assessed by West-ern blotting. Results Compared with the sham group,symptoms of rats in SNL group,such as heat hyperalgesia,mechanical allodynia and poste-rior paws prone to close together,were gradually appeared in the observation time points,with lower spinal proteins expression of CB1(P<0.05). AM841 group exhibited increased proteins expression of CB1 and inhibited SNL-induced heat hyperalgesia and mechanical allodynia(P<0.05). AM281 group further decreased expression of CB1 and amplified the pain abnormality(P<0.05). Conclusion Spinal CB1 participates in the regulation of neuropathic pain,and exogenous cannabinoid CB1 agonists can alleviate the SNL-induced neuropathic pain.

Activation and comparative analysis of cryptic xiamycin gene cluster from marine-derived Streptomyces sp. FXJ 7.388

In order to obtain the natural products synthesized by the three putative xiamycin biosynthesis gene clusters which were predicted via antiSMASH during the genome mining of marine Streptomyces sp. FXJ 7.388, Streptomyces sp. FXJ 8.012, and Streptomyces olivaceus FXJ 7.023. Sixteen genes involved in xiamycin assembly, modification, and regulation with higher identity than the newest reported xiamycin biosynthetic gene cluster from marine Streptomyces sp. SCSIO 02999, Streptomyces sp. HKI0576, and Streptomyces sp. FXJ 7.388 were discovered via gene cluster comparative analysis. A ribosome engineering strategy was adopted to activate such cryptic gene clusters with different final concentrations antibiotics that act on the ribosome, and two indolosesquiterpenes were isolated from idlethaldose streptomycin-resistant Streptomyces sp. FXJ 7.388 strains. However, no such product was detected in Streptomyces sp. FXJ 8.012 and Streptomyces olivaceus FXJ 7.023 under the same treatment. This result suggested that these genes might hold the least gene content for xiamycin biosynthesis

Control status of drinking-water-borne endemic fluorosis in Shaanxi Province: an analysis of survey results / 中华地方病学杂志

Objective To understand the schedule and effectiveness of water-improving defluoridation projects comprehensively in control of fluorosis in drinking-water-borne endemic fluorosis areas in Shaanxi Province,and to provide a scientific basis for making strategies in prevention and control the disease for the next step.Methods The progress of drinking-water-borne endemic fluorosis water-improving defluoridation projects and operation condition were investigated in Shaanxi (fluoride content of drinking water was greater than 1.2 mg/L in the endemic areas) in 2014,and children aged 8 to 12 in 32 epidemic villages of six counties including Jingbian,Dingbian,Dali,Jingyang,Qian and Liquan were selected to survey dental fluorosis.Results In Shaanxi Province,the number of villages with water fluorine content of more than 1.2 mg/L was 5 005 and water improvement rate was 83.42％ (4 175/5 005),water-improving projects operated normally rate was 85.05％ (3 551/4 175),and scraped was 37,accounted for 0.89％ (37/4 175).There were 830 epidemic villages without water-improving projects in Shaanxi Province,and high fluoride exposed population was 579 400,mainly distributed in Yulin,Xianyang,Weinan and Yan'an cities.A total of 1 849 children aged 8 to 12 in the 6 counties were examined,the detection rate of dental fluorosis was 56.57％ (1 046/1 849),the index of dental fluorosis was 1.11.Conclusion In drinking-water-borne fluorosis epidemic areas of Shaanxi,the improved-water rate is generally high,and the normal operation of waterimproving projects is overall good,but the measures for water-improving defluoridation must be reinforced and improved.

Intrathecal injection of oxycodone hydrochloride reduces neuropathic pain in rat model of chronic constriction injury via inhibition of microglial c-JNK/CXCL1 signal / 中国医师杂志

Objective To observe the effect of intrathecal injection (IT) of oxycodone hydrochloride on neuropathic pain and spinal cord level of microglial c-Jun N-terminal kinase/chemokine (C-X-C motif) ligand 1 (c-JNK/CXCL) 1signal in rat model of chronic constriction injury (CCI).Methods Male Sprague-Dawley rats were randomly divided into five groups (n =40 per group):sham group (intrathecal normal saline,IT NS),CCI group (CCI + IT NS),oxy group (CCI + IT 5 μg/30 μl oxy),mino group (CCI + IT 5 μg/30 μl Minocycline),and c-JNK inhibitor group (SP group,CCI + IT 5 μg/30 μl SP600125).The lumbar intrathecal catheters were implanted in L5-6 of rats and CCI models were established as previously described.The thermal and mechanical nociceptive thresholds were assessed by paw withdrawal latency (PWL) to radiant heat and von Frey filaments.The oxycodone,minocycline and SP600125 were administered intrathecally for 3 days before surgery.The spinal cord expression of Ⅰ ba-1,p-c-JNK and CXCL1 proteins assessed by Western blot.Immunofluorescence staining was performed to examine microglia morphology and the number of Ⅰ ba-1 positives cells in dorsal horn of injured spinal cord at 7 days post-IR.Results Compared to sham group,rats in CCI group had significantly lower mechanical and thermal pain thresholds,but higher spinal proteins expression of Ⅰ ba-1,and p-c-JNK and CXCL1 (P ＜0.05).Rats in oxy group,mino group and SP group had significantly higher mechanical and thermal pain thresholds and significantly lower proteins expression of Ⅰ ba-1,p-c-JNK and CXCL1 compared to those in CCI group (at any observed time-point after ligation,but most significantly at 7days,P ＜ 0.05).At the 7days after surgery,microglial cells in CCI group transformed from the ramified shape to amoeboid macrophage-like shape by immunofluorescence staining with the increases of Ⅰ ba-1 positive cells;while the other three groups exhibited hypertrophic morphology with less number Ⅰ ba-1 positive cells (P ＜ 0.05).There were no significant differences between these three groups at any observed time (P ＞ 0.05).Conclusions Intrathecal injection of oxycodone hydrochloride can relieve CCI-induced neuropathic pain by down-regulation microglial c-JNK/CXCL1 signal in spinal cords.Provide new therapeutic targets for clinical treatment of neuropathic pain.

A multicenter research based on data mining technology to analyze traditional Chinese medicine syndromes commonly seen in patients with congestive heart failure / 中国中西医结合急救杂志

Objective To discuss the distribution of traditional Chinese medicine (TCM) syndromes of patients with congestive heart failure (CHF) commonly seen in clinic based on data mining technology.Methods A multicenter study was conducted. 1 451 in-patients with CHF in 4 grade Ⅲ hospitals from December 2010 to September 2012 were enrolled. The cluster and factor methods were applied to synthetically analyze the data concerning the patients' information of four diagnostic methods in TCM, and the TCM syndromes commonly seen in patients with CHF and the preliminary diagnostic scheme were summarized.Results In these 1 451 cases, there were 43 items having been experienced standardization, including clinical symptoms and manifestations of tongue and pulse, and in the information concerning four diagnosis in TCM, there were 14 items whose incidences > 10%. The incidence of chest distress was the highest 89.18% (1 294 cases), followed by shortness of breath 66.16% (960 cases), and the lowest constipation 12.20% (177 cases). There were 4 commonly seen syndromes of CHF as follows: qi deficiency blood stasis syndrome (the major diagnostic bases: palpitation, shortness of breath, dark and red tongue with white fur, thin pulse; and the minor bases: chest distress and thin fur), yang deficiency water diffusion syndrome (major bases: edema of lower limbs, cough, expectoration, difficult urination, chilly, poor appetite, greasy fur, string pulse; minor bases: body strength weakness), phlegm heat obstructing lung syndrome (major bases: chest pain, cough and dyspnea in semi-reclining position, constipation, light tongue with yellow fur, deep, slippery or rapid pulse; minor bases: dizziness), and qi yin deficiency blood stasis syndrome (major bases: dry mouth, night sweating, frequent urination at night, teeth-marked tongue, purplish tongue, uneven or irregular pulse; minor bases: loose stool, headache, purplish lips, swollen tongue with little fur, moderate or weak pulse). The load intervals of each of the symptoms in CHF qi deficiency blood stasis syndrome were from -0.520 to 0.881, all the absolute values were greater than 0.520, and the common degrees extracted were 64.3% - 83.6%, which meant the 5 common factors could extract the original index information all over the common degree 64.3%. In yang deficiency water diffusion syndrome, the load intervals of each of symptoms were from0.732 to 0.983, all the absolute values were greater than 0.732, and the common degrees extracted were 58.2% - 96.9%; in phlegm heat obstructing lung syndrome, the load intervals of each of symptoms were 0.670 - 0.992, the all absolute values were greater than 0.670, and the common degrees extracted were 52.0% - 98.5%. In qi yin deficiency blood stasis syndrome, the load intervals of each of symptoms were 0.576 - 0.926, all the absolute values were greater than 0.576, and the common degrees extracted were 54.2% - 87.1%.Conclusion By application of data mining technology combined with clinical practice, the common TCM syndromes of patients with CHF can be analyzed objectively and comprehensively.

Analysis of monitoring results of coal-burning endemic arsenism in Shaanxi Province in 2010-2014 / 中华地方病学杂志

Objective To investigate the current situation of coal-burning-borne endemic arsenism in the disease affected areas,the usage of anti-arsenism stove and the formation of related behavior;,to evaluate the control effect,so as to provide a basis for development of control strategies.Methods Surveillances were carried out according to the provisions and requirements of The Surveillance Project for Shaanxi Institute Coal-Burning-Borne Endemic Arsenicosis (Trial.).Four villages in two counties of Ankang city and Hanzhong city in Shaanxi Province were monitored in 2010-2014.Using simple random sampling method,10 families in each village were randomly selected to survey the situation of the stove used and related behavior changes.Five households in each village were randomly selected; arsenic level in coal was determined; high arsenic exposed population was investigated according to Endemic Arsenism Diagnostic Criteria (WS/T 211-2001).Urine samples of 30 patients with arsenism were randomly selected to determine the arsenic content.Results The proper utilization rate and the qualified households of improved stoves and iron stoves were all low; the correct drying rate and the correct storage rate of peppers and corns were higher than 95％.The washing rate of corns and peppers before eating were all 100％.A total of 100 copies of coal samples were tested and the arsenism content was between 12.295-455.827 mg/kg,and the geometric mean value of the arsenism content was (91.819 ± 80.989)mg/kg.Seventeen thousand eight hundred and fifty-five individuals were investigated and 1 232 cases of arsenism were diagnosed in the 4 villages; the prevalence rate was 6.90％ (1 232/17 855); urinary arsenism content was between not detected-0.287 mg/L; and the geometric mean value of the arsenic content was 0.033 mg/L.Conclusions The coal-burning-borne endemic arsenism in Shaanxi is in a prevalent state; many anti-arsenism stoves are out of order; and the proper utilization rate is low.To strengthen the disease surveillance,health education and management of anti-arsenism stoves are key measures in control of coal-burning borne endemic arsenism in the future.