Objective:To develop rat models of oral mucosa ulcer using distinct experimental methodologies,fulfilling research requirements and adhering to the ethical standards for animal care.Methods:96 SD rats were randomly allocated into groups.The rats in control group(n=8)were regularly fed without other treatment.Those in chemical cauterization groups were treated by 20％,40％,60％of glacial acetic acid(GAA)on oral mucosa(n=8);in mechanical damage groups by 30 000 r/min high speed drill induced trauma of 10,20 and 30 mm2 respectively(n=8);in ionizing radiation groups were treated with 10,12,15,20 and 30 Gy on the mucosa respectively(n=8).After the ulcer was appeared,the morphology of the mucosa were observed,the mucosal tissue lesions were examined by HE,Masson and immunofluorescence staining,the expression of TNF-α and IL-1β were detected by qPCR and ELISA respectively,and the body conditions such as diet and body weight of the rats were observed,the pain,dis-tress and discomfor of the rats were evaluated by MORTON&Griffits Guidelines.Results:40％and 60％GAA,20 mm2 and 30 mm2 friction damage and ionizing radiation of 12 Gy or greater may induce oral mucosa ulcer with a diseas coruse of 6-7 d in SD rats.TNF-α and IL-1β mRNA expression in the damaged tissue,the related protein expression in blood serum of the rats were in-creased.MORTON&Griffits Guidelines analysis showed 40％GAA,20 mm2 friction damage and 12 Gy ionizing radiation induced the lowest scores of pain,distress and discomfort of the rats with compatible oral mocosa ulcere induced by the relevat treatment.Conclusion:40％GAA,20 mm2 of friction damage and 12 Gy of ionizing radiation can reliably establish oral mucosa ulcer models and minimize adverse effects on SD rats,and accord with ethical standards of 3R for laboratory animal.

Objective To investigate the application of offline solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry for detecting four synthetic cannabinoids(5F-ADB,5F-MDMB-PICA,4F-MDMB-BUTINACA,and MDMB-4en-PINACA)and their marker metabolites in urban wastewater.Methods Samples were pre-treated using an Oasis PRiME HLB column(60 mg,3CC)and analyzed by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry.The mobile phases consisted of 0.02%formic acid-2 mmol/L ammonium formate aqueous solution and acetonitrile solution,with a WATERS ACQUITY UPLCHSS T3 column.Analysis was conducted in positive ionization mode of the ESI ion source,combining multiple reaction monitoring(MRM),information-dependent acquisition(IDA),and enhanced product ion(EPI)scanning modes for qualitative and quantitative analysis of the eight target compounds.Results Good linearity was observed for 4F-MDMB-BUTINACA-M,5F-ADB,5F-ADB-M,and 5F-MDMB-PICA in the concentration range of 1～250 ng/L;for MDMB-4en-PINACA in the range of 5～250 ng/L;and for 4F-MDMB-BUTINACA,5F-MDMB-PICA-M,and 4F-MDMB-BUTINACA-M in the range of 1～500 ng/L.The recovery rates of samples spiked with different concentrations of the eight target compounds ranged from 87.68%to 104.68%,with matrix effects between 88.61%and 112.78%.Both intra-day and inter-day precision were less than 5%.Conclusion The established method demonstrates good accuracy and reproducibility,making it suitable for qualitative and quantitative detection of four synthetic cannabinoids and their metabolites in urban wastewater.

Objective To investigate the application of offline solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry for detecting four synthetic cannabinoids(5F-ADB,5F-MDMB-PICA,4F-MDMB-BUTINACA,and MDMB-4en-PINACA)and their marker metabolites in urban wastewater.Methods Samples were pre-treated using an Oasis PRiME HLB column(60 mg,3CC)and analyzed by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry.The mobile phases consisted of 0.02%formic acid-2 mmol/L ammonium formate aqueous solution and acetonitrile solution,with a WATERS ACQUITY UPLCHSS T3 column.Analysis was conducted in positive ionization mode of the ESI ion source,combining multiple reaction monitoring(MRM),information-dependent acquisition(IDA),and enhanced product ion(EPI)scanning modes for qualitative and quantitative analysis of the eight target compounds.Results Good linearity was observed for 4F-MDMB-BUTINACA-M,5F-ADB,5F-ADB-M,and 5F-MDMB-PICA in the concentration range of 1～250 ng/L;for MDMB-4en-PINACA in the range of 5～250 ng/L;and for 4F-MDMB-BUTINACA,5F-MDMB-PICA-M,and 4F-MDMB-BUTINACA-M in the range of 1～500 ng/L.The recovery rates of samples spiked with different concentrations of the eight target compounds ranged from 87.68%to 104.68%,with matrix effects between 88.61%and 112.78%.Both intra-day and inter-day precision were less than 5%.Conclusion The established method demonstrates good accuracy and reproducibility,making it suitable for qualitative and quantitative detection of four synthetic cannabinoids and their metabolites in urban wastewater.

Objective:To develop rat models of oral mucosa ulcer using distinct experimental methodologies,fulfilling research requirements and adhering to the ethical standards for animal care.Methods:96 SD rats were randomly allocated into groups.The rats in control group(n=8)were regularly fed without other treatment.Those in chemical cauterization groups were treated by 20％,40％,60％of glacial acetic acid(GAA)on oral mucosa(n=8);in mechanical damage groups by 30 000 r/min high speed drill induced trauma of 10,20 and 30 mm2 respectively(n=8);in ionizing radiation groups were treated with 10,12,15,20 and 30 Gy on the mucosa respectively(n=8).After the ulcer was appeared,the morphology of the mucosa were observed,the mucosal tissue lesions were examined by HE,Masson and immunofluorescence staining,the expression of TNF-α and IL-1β were detected by qPCR and ELISA respectively,and the body conditions such as diet and body weight of the rats were observed,the pain,dis-tress and discomfor of the rats were evaluated by MORTON&Griffits Guidelines.Results:40％and 60％GAA,20 mm2 and 30 mm2 friction damage and ionizing radiation of 12 Gy or greater may induce oral mucosa ulcer with a diseas coruse of 6-7 d in SD rats.TNF-α and IL-1β mRNA expression in the damaged tissue,the related protein expression in blood serum of the rats were in-creased.MORTON&Griffits Guidelines analysis showed 40％GAA,20 mm2 friction damage and 12 Gy ionizing radiation induced the lowest scores of pain,distress and discomfort of the rats with compatible oral mocosa ulcere induced by the relevat treatment.Conclusion:40％GAA,20 mm2 of friction damage and 12 Gy of ionizing radiation can reliably establish oral mucosa ulcer models and minimize adverse effects on SD rats,and accord with ethical standards of 3R for laboratory animal.

The incidence and mortality of digestive system tumors are increasing year by year,which seriously threatens human life and health.In recent years,it has been found that long noncoding RNA(lncRNA)is involved in regulating the proliferation,migration,and invasion of digestive system tumors.This article reviewed the progress of research on lncRNA in digestive system tumors.

The incidence and mortality of digestive system tumors are high,and the trend is increasing year by year,and the early onset is hidden,difficult to detect,and seriously threaten human health.In recent years,it has been found that long noncoding RNA(lncRNA),as a new class of non-coding RNA,plays an important role in the occurrence and development of tumors,influencing the occurrence and development of tumors by regulating the malignant biological characteristics of tumor cells such as proliferation,invasion and metastasis.Further study on the role of lncRNA in digestive system tumors can further discover its diagnosis and treatment methods,and provide new ideas for reducing the incidence and mortality of digestive system tumors.This article reviewed the progress of research in lncRNA in digestive system tumors.

【Objective】 To investigate the effects of 80 kVp combined with multi-model adaptive statistical iterative reconstruction algorithm （ASiR-V） on the image quality of CT angiography （CTA） of iliac artery in kidney transplantation candidates before operation. 【Methods】 Totally 50 kidney transplantation candidates underwent “one-stop” scanning combined CTA for coronary and iliac arteries were recruited consecutively. After the scanning， images were reconstructed with different ASiR-V levels on the iliac artery from 50% to 100% at a 10% interval， and 6 groups of images were obtained. We evaluated and compared all image qualities， DLP and CTDI in the patients’ examination were recorded， and the effective dose （ED） was calculated. 【Results】 All of the image quality objective scores of different ASiR-V levels on the iliac artery were above 3 points （3.32±0.24）， and the average CT value was （344.30±74.53）HU. The ED received by the patient throughout the examination was （2.71±0.42)mSv. The image noise decreased while SNR and CNR increased monotonically as the ASiR-V levels increased， among which 80% ASiR-V image quality score was the highest with 3.41±0.26. 【Conclusion】 For patients who need to have both coronary and iliac arteries evaluated before kidney transplantation operation， low tube voltage （80 kVp） combined with 80% ASiR-V can obtain high-quality iliac artery images under the premise of reducing the ED dose， which can provide practical basis for further reducing the dose in personalized scanning scheme for such patients. It has good feasibility and clinical application value.

Objective:To investigate the clinicopathological characteristics and the therapeutic effects of signet ring cell carcinoma (SRCC) of rectum and sigmoid colon.Methods:Clinical data and the follow-up information of 29 SRCC patients treated in our tertiary care center from 2008 to 2018 were retrospectively reviewed. The clinicopathological features, diagnostic and therapeutic effects, and the prognostic outcomes were analyzed.Results:Among the 29 patients, 17 were male, 12 were female. The average age was (48.7±14.3) years. Colonoscopy revealed the features of diffuse circumferential thickening of the bowel wall in 20/29 cases (69.0%), while in 9/29 cases (31.0%), endoscopic biopsies showed false negative results. Twenty-five% (4/16) and 17.6% (3/17) lesions were misdiagnosed as the inflammatory changes by endoscopic rectal ultrasonography exam and rectal MRI scan, respectively. Thirteen of the 29 patients received the neoadjuvant chemoradiotherapy (NCRT), 27 patients underwent the radical resection surgeries, and 8 underwent the postoperative radiotherapy. With a median follow-up of 38.5 (3.5-87.0) months, the cumulative 3-years overall survival (OS) rate was 54.0%, and the cumulative 3-years disease-free survival (DFS) rate was 43.0%. The OS rates of patients treated with or without NCRT (non-NCRT) were 46.2% and 69.2%, respectively, without significant difference ( P>0.05). The DFS rates of patients treated with or without NCRT were 45.8% and 39.2%, respectively, without significant difference ( P>0.05). Parameters including age younger than 40 years and tumor size larger than 5 cm were independent potential risk factors for shortened OS ( P<0.05). Conclusions:SRCC of the rectum and sigmoid colon is a rare malignant tumor with special clinical manifestations. It is younger-onset, highly malignant and with very poor prognosis. Therefore, in-depth researches with focus upon the progress of molecular oncology are urgently needed to substantially improve the therapeutic effect of this disease.

Objective:To investigate the clinicopathological characteristics and the therapeutic effects of signet ring cell carcinoma (SRCC) of rectum and sigmoid colon.Methods:Clinical data and the follow-up information of 29 SRCC patients treated in our tertiary care center from 2008 to 2018 were retrospectively reviewed. The clinicopathological features, diagnostic and therapeutic effects, and the prognostic outcomes were analyzed.Results:Among the 29 patients, 17 were male, 12 were female. The average age was (48.7±14.3) years. Colonoscopy revealed the features of diffuse circumferential thickening of the bowel wall in 20/29 cases (69.0%), while in 9/29 cases (31.0%), endoscopic biopsies showed false negative results. Twenty-five% (4/16) and 17.6% (3/17) lesions were misdiagnosed as the inflammatory changes by endoscopic rectal ultrasonography exam and rectal MRI scan, respectively. Thirteen of the 29 patients received the neoadjuvant chemoradiotherapy (NCRT), 27 patients underwent the radical resection surgeries, and 8 underwent the postoperative radiotherapy. With a median follow-up of 38.5 (3.5-87.0) months, the cumulative 3-years overall survival (OS) rate was 54.0%, and the cumulative 3-years disease-free survival (DFS) rate was 43.0%. The OS rates of patients treated with or without NCRT (non-NCRT) were 46.2% and 69.2%, respectively, without significant difference ( P>0.05). The DFS rates of patients treated with or without NCRT were 45.8% and 39.2%, respectively, without significant difference ( P>0.05). Parameters including age younger than 40 years and tumor size larger than 5 cm were independent potential risk factors for shortened OS ( P<0.05). Conclusions:SRCC of the rectum and sigmoid colon is a rare malignant tumor with special clinical manifestations. It is younger-onset, highly malignant and with very poor prognosis. Therefore, in-depth researches with focus upon the progress of molecular oncology are urgently needed to substantially improve the therapeutic effect of this disease.

Dry powder inhalers (DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance. The purpose of this review is to summarize and illuminate how these factors affect drug-carrier interaction and influence the performance of DPIs.