OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

BACKGROUND: Limited data are available on the comparison of clinical outcomes of complete vs. incomplete percutaneous coronary intervention (PCI) for patients with chronic total occlusion (CTO) and multi-vessel disease (MVD). The study aimed to compare their clinical outcomes. METHODS: A total of 558 patients with CTO and MVD were divided into the optimal medical treatment (OMT) group ( n = 86), incomplete PCI group ( n = 327), and complete PCI group ( n = 145). Propensity score matching (PSM) was performed between the complete and incomplete PCI groups as sensitivity analysis. The primary outcome was defined as the occurrence of major adverse cardiovascular events (MACEs), and unstable angina was defined as the secondary outcome. RESULTS: At a median follow-up of 21 months, there were statistical differences among the OMT, incomplete PCI, and complete PCI groups in the rates of MACEs (43.0% [37/86] vs. 30.6% [100/327] vs. 20.0% [29/145], respectively, P = 0.016) and unstable angina (24.4% [21/86] vs. 19.3% [63/327] vs. 10.3% [15/145], respectively, P = 0.010). Complete PCI was associated with lower MACE compared with OMT (adjusted hazard ratio [HR] = 2.00; 95% confidence interval [CI] = 1.23-3.27; P = 0.005) or incomplete PCI (adjusted HR = 1.58; 95% CI = 1.04-2.39; P = 0.031). Sensitivity analysis of PSM showed similar results to the above on the rates of MACEs between complete PCI and incomplete PCI groups (20.5% [25/122] vs. 32.6% [62/190], respectively; adjusted HR = 0.55; 95% CI = 0.32-0.96; P = 0.035) and unstable angina (10.7% [13/122] vs. 20.5% [39/190], respectively; adjusted HR = 0.48; 95% CI = 0.24-0.99; P = 0.046). CONCLUSIONS For treatment of CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina, as compared with incomplete PCI and OMT. Complete PCI in both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.
Humans ; Treatment Outcome ; Percutaneous Coronary Intervention/methods* ; Coronary Occlusion/surgery* ; Prognosis ; Angina, Unstable/surgery* ; Chronic Disease ; Risk Factors

Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.

Objective To investigate the effect of lycium barbarum polysaccharides (LBP) on apoptosis and autophagic death in primary cultured hippocampal neurons after oxygen glucose deprivation and reoxygenation (OGD/R) injury.Methods Primary cultured hippocampal neurons were exposed to OGD/R.The cells were randomly divided into 5 groups:control group,OGD/R group,and OGD/R+LBP groups (15,30 and 60 μg/mL LBP).The cell viability was assessed by MTT assay.The cell damage was evaluated through detecting the lactate dehydrogenase (LDH) release rate.Apoptosis rate was detected by TUNEL,and cleaved Caspase-3 was identified by immunofluorescence staining.Protein expression was detected by Western blotting.Results As compared with the control group,OGD/R group had significantly decreased cell viability (P＜0.05);and significantly increased cell viability and decreased LDH release rate were noted in the LBP (15,30 and 60 μg/mL) treatment groups as compared with those in the OGD/R group (P＜0.05).The 60 μg/mL LBP treatment group had significantly smaller number of TUNEL-positive cells than the OGD/R group(P＜0.05).Immunofluorescence staining and Western blotting both revealed that 60 μg/mL LBP treatment group had significantly decreased Beclinl level and ratio of cleaved Caspase-3/Caspase-3 and ratio of microtubule-associated protein light chain (LC)3 Ⅱ/LC3Ⅰ,and statistically increased p62 level and ratio of Bcl-2/Bax as compared with OGD/R group (P＜0.05).Conclusion LBP treatment protects primary hippocampal neurons from OGD/R injury via inhibiting apoptosis and autophagic cell death.

This is a complicated and difficult case. The onset symptom of a 62-year-old male was recurrent intestinal obstruction. Ileocecal and ileocolic operation was done twice. Massive gastrointestinal bleeding occurred due to giant fistula of descending duodenum, which connected to ileocolic anastomosis. After consultation by multidisciplinary team, jejunal-feeding tube was placed to provide enteral nutrition. With general condition improving, duodenal fistula repair and involved bowel resection were performed. Postoperative pathology confirmed Crohn's disease. The patient was treated with thalidomide and recovered well during follow-up.

Objective To clarify the clinical features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) with minor endoscopic abnormalities. Methods The clinical data of 6 patients with MEITL characterized by minor endoscopic abnormalities in Peking Union Medical College Hospital from 2012 to 2016 were retrospectively analyzed, including clinical manifestations, endoscopic, pathological features, medications and prognosis. Results Five out of 6 patients were male, with an average age of 61.2 years old. The median disease duration was 4.5 months. All patients initially presented with diarrhea without specific findings for serologic testing. CT enterography showed continuous intestinal lesions, including symmetric thickening of the bowel wall, abnormal hyperenhancement of mucosal surface and lymphadenopathy. Endoscopic appearances were only mildly abnormal, including mucosal swelling, atrophy of villus, mosaic sign and shallow ulcers. Histopathologic findings revealed massive small to medium sized T lymphocytes infiltration with positive expression of CD3 and CD8. Chemotherapy and palliative treatment were administrated after diagnosis. Conclusions Clinical presentations of MEITL are non-specific with minor endoscopic abnormalities. Therefore, biopsy is indispensable for patients with a relatively normal endoscopic result.

Objective To study the diagnostic value of magnifying chromoendoscopy combined with narrow band imaging (NBI) for screening inflammatory bowel disease (IBD) and colorectal cancer(CRC).Methods In colonoscopic examinations of long-term IBD patients,magnifying colonoscopy was used to make the consecutive observation with white light,NBI,and indigo carmine spraying.Targeted biopsies or endoscopic resections were performed for histological diagnosis as the golden standard of this study.Results Sixteen cases (17 lesions) with dysplasia or colorectal cancer in 45 long-term IBD patients were detected,including 12 (26.7％) cases of low-grade dysplasia (LGD),4 (8.9％) cases of high-grade dysplasia (HGD),and 1 (2.2％) case of CRC.Targeted biopsy yielded a positive rate of 13.2％ (17/129).Detection rates of NICE and Kudo classification were 81.3％ (13/16) and 75.0％ (12/16),respectively,and were 100.0％ when combined together.Age (P =0.027) and prolonged disease course (P =0.013)were associated with advanced histology in those with dysplasia or CRC.Lesions of HGD and CRC have larger diameters (2.5 ± 1.4 cm) than LGD (0.6 ± 0.4 cm) (P =0.003).Conclusion Magnifying chromoendoscopy with NBI is effective to detect and differentiate colitis-related neoplastic lesions,thus allowing rational therapeutic plans.

Objective To differentiate colorectal sessile serrated adenoma(SSA)and large hyperplastic polyp(HP)with white light endoscopy and narrow band imaging. Methods Retrospective analysis was performed on the clinical data of 953 patients who underwent endoscopic screening for colorectal cancer at digestive endoscopy center of Peking Union Medical College Hospital from January 2015 to December 2015.Endoscopic features were compared with white light endoscopy and narrow band imaging between SSA and large HP in location, size, Paris classification, surface mucus, NICE classification and varicose microvascular vessel(VMV). Results A total of 28(2.9%)SSAs and 25(2.6%)HPs of diameter not less than 0.5 cm were detected in the total of 953 patients.Statistically significant difference was found in right hemi-colon, diameter not less than 1.0 cm and VMV in two groups(P<0.05). The sensitivities of the above three markers for SSA were 89.3%, 67.9% and 46.4% respectively. The specificities were 64.0%,76.0% and 84.0% respectively. Diagnostic accuracies were 77.4%,71.7% and 64.2% respectively. And the sensitivity, specificity and accuracy of three markers combined(at least two markers)were 75.0%, 88.0% and 81.1%, respectively. Conclusion SSA and large HP could be differentiated with a systemic consideration of lesion location, size, and surface of microvessels by using white light endoscopy and image-enhanced technique.

Objective To assess the fecal immunochemical test (FIT) followed by colonoscopy in opportunistic screenings for colorectal neoplasm.Methods Total 6 193 patients, who underwent opportunistic colorectal cancer (CRC) screening, were classified into four groups: 3 812 patients underwent direct colonoscopy (group 1), 1 244 patients received one FIT followed by colonoscopy (group 2), 341 patients received two FITs followed by colonoscopy (group 3), and 796 patients received three FITs followed by colonoscopy (group 4).Results Total 97 (1.6%) patients with CRC and 1 038 (16.8%) with colorectal adenoma were detected.The positive predictive value of 1, 2 and 3 positive tests out of three FITs for CRC were 4.53%, 5.62% and 8.94%, respectively, which was higher than that of direct colonoscopy (1.52%).One or more positive tests out of three FIT had the largest area under receiver operating characteristic curve (0.743).For colorectal adenoma, detection rate of direct colonoscopy (17 581.25/105) was higher than all FIT strategies (3 732.30/105-13 127.41/105).Conclusions Single or repeated FIT and colonoscopy have different screening utility.One or more positive tests out of three FIT followed by colonoscopy is preferred to screen CRC, and direct colonoscopy is better for detection of colorectal adenoma.

Objective To investigate the rational program of colorectal cancer(CRC)screening between ages and genders by using single or repeated fecal immunochemical test(FIT)and colonoscopy. Methods Data of 6 193 patients who underwent opportunistic CRC screening at Peking Union Medical College Hospital were retrospectively analyzed.Patients were divided into four groups:(1)direct colonoscopy;(2)one FIT followed by colonoscopy;(3)two FITs followed by colonoscopy;(4)three FITs followed by colonoscopy.Cost-effectiveness of the four screening procedures was compared between different age groups and genders.Results Ninety-seven(1.6%)patients with CRC and 1 038(16.8%)with colorectal adenoma were detected. In patients younger than 40 years old,1-3 positive FIT strategies were superior to direct colonoscopy. In men aged 40 to 60,one or two positive FITs out of three was more cost-effective than direct colonoscopy,so was one positive FIT out of three in women aged 40 to 60. Direct colonoscopy was the most cost-effective strategy in men older than 60,while one positive FIT out of two was the best screening choice in women older than 60. Conclusion Age and gender are two influential factors for cost-effectiveness of CRC screening. Direct colonoscopy is the most cost-effective screening strategy for men older than 60,but one or more positive FIT followed by colonoscopy is preferred in other age and gender groups.