Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

Objective:To discuss the medication law in prescriptions of Professor Shao Nianfang in the treatment of kidney deficiency and bone marrow loss in senile dementia based on data mining.Methods:Medical cases of kidney deficiency and bone marrow loss in senile dementia in the Geriatric Hospital of Shandong University of Traditional Chinese Medicine from 1st Jan. 2014 to 31st Oct, 2019 were collected. Through hospital electronic medical records system prescription statistics, using ancient and modern medical case cloud platform (V1.2.4), medication frequency, property ans taste, efficacy analysis, correlation rule analysis, clustering analysis and complex network analysis were performed.Results:Totally 110 cases were included in medical cases, involving 238 kinds of Chinese materia medica. The top 10 Chinese materia medica with use frequency were Poria, Acori Tatarinowii Rhizoma, Corni Fructus, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Alpiniae Oxyphyllae Fructus, Rehmanniae Radix, Astragali Radix, Chuanxiong Rhizoma, Atractylodis Macrocephalae Rhizoma; the properties were mainly mild, warm slight cold, and cold; the tastes were mainly sweet, bitter, pungent, and light; the meridians were mainly spleen, liver, lung and kidney meridians; the efficacy was clearing dampness and promoting diuresis, clearing heat and promoting blood circulation, calming mind, clearing heat and detoxification, reducing dampness and promote appetizing, tonifying spleen; the association analysis found 15 groups of drug combinations used more than 25 times, they were: Corni Fructus and Poria, Corni Fructus and Dioscoreae Rhizoma, Dioscoreae Rhizoma and Corni Fructus, Rehmanniae Radix Praeparata and Corni Fructus, Dioscoreae Rhizoma and Poria, Astragali Radix and Poria, Alismatis Rhizoma and Poria, Moutan Cortex and Poria, Rehmanniae Radix Praeparata and Poria, Rehmanniae Radix and Poria, Polygalae Radix and Acori Tatarinowii Rhizoma, Moutan Cortex and Corni Fructus, Moutan Cortex and Dioscoreae Rhizoma, Alismatis Rhizoma and Corni Fructus, Alismatis Rhizoma and Dioscoreae Rhizoma; clustering analysis identified four groups of new prescriptions, the first group: Poria, Rehmanniae Radix, Rehmanniae Radix Praeparata, Alismatis Rhizoma, Moutan Cortex, Corni Fructus, Dioscoreae Rhizoma; the second group: Acori Tatarinowii Rhizoma, Cistanches Herba, Morindae Officinalis Radix; the third group: Alpiniae Oxyphyllae Fructus, Chuanxiong Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle; the fourth group: Atractylodis Macrocephalae Rhizoma, Codonopsis Radix, Astragali Radix, Angelicae Sinensis Radix; the results of complex network analysis showed that the core prescription was modified Liuwei Dihuang Pills. Conclusion:This study found that in view of kidney deficiency and bone marrow loss in senile dementia, Professor Shao pays attention to strengthening the healthy qi, and focuses on tonifying deficiency, taking into account the methods of clearing dampness, clearing heat, detoxification, removing blood stasis and restoring consciousness. The four new prescriptions found in the study can provide a reference for modified medication for syndrome differentiation.

Background: Crawling-type gastric adenocarcinoma is a rare subtype of gastric cancer, however, the understanding on this special entity of gastric cancer is still lacking. Aims: To investigate the clinical, endoscopic and pathological characteristics of crawling-type early gastric adenocarcinoma. Methods: Patients diagnosed as crawling-type early gastric adenocarcinoma in Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to December 2021 were recruited consecutively in a retrospective study. The clinical data were reviewed, the pathological specimens were collected for immunohistochemical staining, and a telephone follow-up was conducted for prognosis analysis. Results: Fourteen patients with crawling-type early gastric adenocarcinoma and fulfilling the inclusion criteria were enrolled in the study, of them, 9 were male, 5 were female, and the mean age was 65.9 years old. No family history of gastric cancer was reported. The clinical manifestations were not specific. All patients were positive for Helicobacter pylori (Hp) infection. Tumors were more likely to occur in the middle and lower thirds of the stomach, with marked atrophic background mucosa. Macroscopically, 11 lesions were superficial-depressed (0-IIc) and 3 were superficial-flat type (0-IIb+ IIc). The color of the lesions was red. Lesions with indistinct border were observed endoscopically in 10 cases. Complete resection was achieved in all 14 patients after endoscopic submucosal dissection n=10 or surgical treatment n=4. Three submucosal and 11 intramucosal infiltration were observed pathologically. Immunohistochemical results of gastric (MUC5AC and MUC6) and intestinal (MUC2, CD10 and CDX-2) markers showed that most of the patients were mixed immunophenotype; the Ki-67 index ranged mostly between 30% and 70%. In a mean follow-up time of 38 months, all 14 patients were survived. Two patients with heterochronous early gastric cancer were found by follow-up endoscopy. Conclusions: When a superficial-depressed or superficial-flat type tumor with reddish color change and atrophic background mucosa is observed endoscopically in an Hp-positive patient, the possibility of crawling-type early gastric adenocarcinoma should be considered. Adequate preoperative evaluation should be carried out to judge the extent and depth of tumor invasion, which may guide the decision of treatment strategy. Postoperative endoscopic surveillance is recommended.

ObjectiveTo explore the anhedonia level and its relationship with cognitive function in patients with first-episode psychosis， and to analyze the influencing factors of cognitive function. MethodsA total of 143 first-episode psychiatric patients who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） in the Affiliated Brain Hospital of Guangzhou Medical University from December 2016 to March 2019 were selected. Positive and Negative Syndrome Scale （PANSS） was used to evaluate the patient’s psychiatric symptoms， in which N2 （emotional withdrawal） and N4 （passive/apathetic social withdrawal） were used to assess the anhedonia level， and patients whose （N2+N4） scores beyond 4 were classified into anhedonia group， and those with （N2+N4） scores less than or equal to 4 were classified into non-anhedonia group. Hamilton Depression Scale-24 item （HAMD-24） was used to measure the depressive symptoms， and the MATRICS Consensus Cognitive Battery （MCCB） was used to detect cognitive function. Then the clinical symptoms and cognitive function of two groups were compared， and the influencing factors of cognitive function were screened by multiple linear regression analysis. ResultsThe negative symptom score， general pathological symptom score and total score of PANSS in anhedonia group were significantly higher than those of non-anhedonia group， with statistical difference （P<0.05）. The score of working memory in adolescent subgroup， the scores of information processing speed， attention/alertness and vocabulary learning in adult subgroup of anhedonia group were lower than those of non-anhedonia group， with statistical difference （P<0.05）. Multiple linear regression analysis showed that the anhedonia score and the duration of untreated psychosis were the influencing factors of working memory in adolescent subgroup （P<0.05）. ConclusionPatients with high levels of anhedonia suffer more severe mental symptoms and cognitive impairment， moreover， anhedonia is one of the influencing factors of working memory in adolescents.

Objective:To investigate the risk factor of renal anemia in maintenance hemodialysis patients (MHD) and the association of N-terminal pro-brain natriuretic (NT-proBNP) level with renal anemia.Methods:Patients who received MHD for more than 3 months at Huashan Hospital affiliated to Fudan University from August 2018 to November 2018 were selected as the subjects. The patients were divided into anemia group and non-anemia group according to the hemoglobin level. The patients' general data, the laboratory examination and dialysis related data during the observation period were collected. Pearson correlation analysis was used to analyze the correlation between anemia indicators, dialysis-related indicators and blood NT-proBNP levels. Stepwise multiple linear regression analysis was used to analyze the risk factors for anemia in MHD patients.Results:A total of 160 patients with MHD were included in this study, aged (63.11±11.35) years. There were 79 males (49.4%) and 81 females (50.6%). The dialysis age was (118.01±82.32) months, hemoglobin was (110.09±13.48) g/L, and the median NT-proBNP was 3 985 ng/L. There were 73 cases (45.6%) in anemia group and 87 cases (54.4%) in non-anemic group, and NT-proBNP levels were significantly higher in anemia group than that in the non-anemia group ( t=-3.714, P<0.001). Hemoglobin levels were positively correlated with weekly dialysis time ( r=0.228) and albumin ( r=0.349), and negatively correlated with NT-proBNP levels ( r=-0.318). Hematocrit was positively correlated with weekly dialysis time ( r=0.283), serum calcium ( r=0.317), phosphorus ( r=0.264) and albumin ( r=0.513) with significance (all P<0.05). Univariate regression analysis showed that the level of ln (NT-proBNP) was negatively correlated with hemoglobin ( P<0.001). Stepwise multiple linear regression results showed that low albumin level and high NT-proBNP level were independent risk factors for renal anemia in MHD patients. Conclusions:The increase level of NT-proBNP in MHD patients is independently associated with the decrease level of hemoglobin. Low albumin level and high NT-proBNP level are risk factors for renal anemia, suggesting that the treatment of renal anemia needs to consider improving the factors such as malnutrition and high volume.

Objective:To investigate the influence of indoxyl sulfate(IS), a typical protein-bound uremic toxin, on left atrial (LA) functional strains using three-dimensional speckle tracking echocardiography (3DSTE).Methods:From May 2019 to January 2020, 128 individuals were consecutively enrolled, including 37 healthy controls and 91 patients, who received maintenance hemodialysis (MHD) in the blood purification center of Zhongshan Hospital affiliated to Fudan University. Conventional echocardiographic parameters and 3DSTE datas of LA were obtained on interdialytic days.LA reservoir, conduit and contraction strains (LASr, LAScd and LASct) were calculated and compared. IS concentration in plasma was assessed by high-performance liquid chromatography tandem mass spectrometry in the MHD cohort.According to the IS concentration, the MHD group was divided into high and low IS (HI and LI) groups. The LA data were also compared between the two groups and linear regression analysis was used to identify independent impact factors of LA strains.Results:Compared to the control group, MHD group had markedly enlarged LA volumes( P<0.05). With regard to the LA phasic strains, both of LASr and LAScd were decreased( P<0.05), while LASct remained unchanged( P>0.05). Compared to the LI group, LASr, LAScd and LASct of the HI group were significantly decreased(all P<0.05). Correlation analysis showed IS concentration correlated well with LASr( rs=-0.674, P<0.001), LAScd( rs=0.454, P<0.001) and LASct( rs=0.376, P<0.001). After adjustment of age, systolic blood pressure, left ventricular mass index(LVMI), and pulmonary systolic pressure, IS concentration remained independently associated with LASr (β=-0.206, 95% CI=-0.353--0.059, P=0.007). Conclusions:In MHD patients, LA is enlarged, and its reservoir function and conduit function are impaired.LA strains derived from 3DSTE are independently related to the IS concentration in plasma, which can be used for the monitoring and evaluation of IS induced cardiac injury.

Objective To construct a knowledge system of cultural competence education among undergraduate nursing students, so as to enhance the cultural capacity of undergraduate nursing students. Methods From September 2015 to January 2016, a two-round expert consultation was conducted among 11 nursing experts who engaged in multicultural related work in Shanghai, Hangzhou and other places by Delphi method. Results The active coefficient of the two rounds of the expert consultation were both 100%. The expert authority (Cr) was 0.89, and the coordination coefficients of the first and second round of consultation were 0.227 and 0.236 respectively (P<0.01). Finally, the knowledge system of cultural competence education in undergraduate nursing students was constructed, including 5 first-level indicators, 10 second-level indicators and 39 third-level indicators. Conclusions The primarily constructed knowledge system of cultural competence education among undergraduate nursing students is a scientific and reasonable frame work system, which provides content references and evaluation basis for the cultural competence education among undergraduate nursing students in our country.

Objective To evaluate the impact of maintenance hemodialysis(MHD) on left ventricular(LV) strains via layer-specific speckle-tracking imaging (LSTI).Methods Twenty-eight MHD patients and 28 matched controls were enrolled in the study.Conventional echocardiography and LSTI were performed on patients before and shortly after one hemodialysis session,as well as on controls.Results LV end-diastolic volume (LVEDV) were markedly reduced after one session of HD [(52.3±22.4)ml/m2 vs (55.0±15.3)ml/m2,P=0.033],but still larger than the control group (47.4±6.4) ml/m2.LV ejection fraction (LVEF) decreased in MHD patients after HD [(62.5±8.1)% vs (64.6±7.3)%,P=0.06],which was similar to those in the control group (66.0±4.2)% and in MHD patient before HD (P=0.391).The three layer circumferential and longitudinal strains decreased in the order of the control group,patients before HD and after HD [CS-endo:(-26.3±3.6)% vs (-22.2±4.7)% vs (-19.2±5.4)%;CS-mid:(-19.0±2.7)% vs (-15.3±3.5)% vs (-13.0±3.8)%;CS-epi:(-11.1±2.3)% vs (-8.0±2.6)% vs (-6.5±2.3)%;LS-endo:(-23.7±3.0)% vs (-18.6±3.6)% vs (-16.4±4.5)%;LS-mid:(-20.9±2.7)% vs (-16.3±3.1)% vs (-14.0±4.1)%;LS-epi:(-18.4±2.4)% vs (-14.1±2.8)% vs (-12.0±3.6)%;all P<0.01],while the synchrony index,standard deviation of times to peak longitudinal strain,increased in these three groups [(3.6±1.0)% vs (6.3±1.5)% vs (7.5±2.2)%,all P<0.01].Linear correlation analysis showed ultrafiltration volume was negatively related with the difference of longitudinal strains before and after HD (difference of LS-endo:r=-0.428,P=0.023;difference of LS-mid:r=-0.423,P=0.025;difference of LS-epi:r=-0.422,P=0.025).Conclusions One session of HD may have injurious effects on LV strains and systolic synchrony.The reduction of ultrafiltration volumes may be helpful to protect cardiomyocytes.

Objective To explore the curative effect of quetiapine combined with paroxetine in the treatment of bipolar depression,and to provide reference for the choice of clinical treatment.Methods According to the digital table,96 patients with bipolar disorder were randomly divided into observation group and control group,48 cases in each group.The control group was treated with quetiapine orally,the observation group was treated with quetiapine combined with paroxetine.After 6 weeks of treatment,the clinical curative effect,the Montgomery Asberg Depression Rating Scale and the Beck pull fan Sen Mania Rating table score before and after treatment were compared between the two groups.At the same time,the adverse reactions of the two groups were compared.Results After 6 weeks of treatment,the total effective rate of the observation group was 70.83％,which was significantly higher than 50.00％ in the control group,the difference was statistically significant(x2 =4.356,P =0.037).After 6 weeks of treatment,the Montgomery Asberg Depression Rating quantity score in the observation group was (14.01 ± 2.95) points,which was significantly lower than (18.07 ± 3.05)points in the control group,the difference was statistically significant (t =5.527,P =0.036).The Baker-pull fan Sen Mania Rating score before and after treatment between the two groups had no statistically significant differences.There were no serious adverse reactions in the two groups.Conclusion Quetiapine combined with paroxetine can effectively inhibit bipolar depressive episodes,avoid manic episodes,has good clinical efficacy and high safety,it is worthy of popularization and application.