each group were sacrificed, respectively. Distributions of BrdU positive cels and ChAT positive cels were detected by S-P immunohistochemical method. The learning and memory abilities of rats were detected by Morris water maze system.
RESULTS AND CONCLUSION:BrdU positive cels were mainly distributed in the cortex and hippocampus, especialy around the blood vessels, and there was the presence of focal aggregation. A smal amount of BrdU positive cels were observed in the basal ganglia and thalamus as wel as in the ependyma. BrdU positive cels were counted at different time after operation. The number of BrdU positive cels decreased with time, and only a smal number of BrdU positive cels were observed at 60 days after transplantation. The number of ChAT positive cels at different time after transplantation was ranked as folows: neural stem cel transplantation group > model group > sham operated group (P < 0.05). Compared with the model group, the time for searching the platform was significantly lower in the neural stem transplantation group and sham operated group, but the number of crossing the platform was significantly higher in the neural stem cel transplantation group and sham operated group (P < 0.05). The results show that neural stem cels could be transplanted into the rats with vascular dementia, and the cels could survive and migrate in the brain of rats and significantly improve the learning and memory ability. This mechanism may be related to the differentiation and growth of cholinergic neurons in the hippocampus.

Objective To investigate the changes and significance of serum inflammatory factors in coronary heart disease (CHD) patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) ,and the treatment effects of continuous positive airway pressure (CPAP).Methods A total of 76 CHD patients in Renmin Hospital of Wuhan University from October 2007 to October 2008 were enrolled.Polysomnography (PSG) was performed in these CHD patients to identify if they were complicated by OSAHS.The levels of inflammatory factors including TNF-α, IL-6, high sensitive C-reactive protein (hs-CRP) in serum were determined in the CHD patients and 23 normal subjects.The CHD patients with mederate-severe OSAHS (AHI≥ 15 episodes/hour) were treated by Auto-CPAP for 3 months and all parameters above were measured again.Results There were 41/76 (53.9%) of CHD patients had mederate-severe OSAHS and were treated with CPAP.The levels of TNF-ct,IL-6 and hs-CRP were significantly higher in the CHD patients than those in the normal controls (all P <0.01) ,and were significantly higher in moderate-severe OSAHS patients than those in the non-OSAHS CHD patients.Auto-CPAP ventilation significantly decreased the levels of inflammatory factors in the CHD patients with moderate-severe OSAHS.Conclusions An obvious proinflammatory state is detected in CHD patients ,and is aggravated with OSAHS.CPAP is a useful treatment for CHD patients with mediate to severe OSAHS.

Aim To investigate the effect of Ajuga decumbens(HBG), Poria cocos(FL) and their combination on the metastasis of invasive breast cancer cells and the related mechanisms.Methods We conducted several assays including cell adhesion assay, scratch assay and transwell invasion assay.Western blot analysis was employed to detect the expression of associated proteins of EMT and MAPK signaling pathway.Results FL,HBG and their combination could significantly inhibit the adhesion, migration and invasion of MDA-MB-231 and SK-BR-3 cells.HBG and FL had markedly synergistic effect, and the best compatibility ratio was 10 ∶1.HBG, FL and their combination could reverse EMT of breast cancer cells, which increased the levels of epithelial biomarkers, such as β-catenin, E-cadherin and ZO-1, and reduced the levels of mesenchymal biomarkers, such as vimentin.Moreover, treatment of the cells with HBG, FL and their combination resulted in marked inhibition of phosphorylation of ERK1/2, JNK and p38.Conclusions The combination of HBG and FL have the ability to inhibit breast cancer cell invasion by targeting the expression of MAPK pathway as well as suppressing the epithelial-to-mesenchymal transition.

Objective To evaluate the effect of breathing exercise program (shrinking lips abdominal breathing combined with vertical breathing gymnastics) on dyspnea, pulmonary function, exercise tolerance and quality of life in patients with moderate to severe chronic obstructive pulmonary disease(COPD). Methods A total of 90 hospitalized patients with moderate to severe COPD were randomly divided into the experimental group and the control group with 45 cases in each group. The experimental group lost one case and the control group lost three cases, 86 patients finished the experiment. During hospitalization, on the base of conventional treatment and care, the experimental group
received training of shrinking lips abdominal breathing combined with vertical breathing gymnastics after medical staff′s care, with folk music as the background. Exercise frequency:morning, afternoon, 2 times per day, 15 min per time and continue to exercise with researchers′ guidance after discharge. In the control group:take exercises by self, take routine follow-up after discharge. The intervention continued for three months. The indicators such as dyspnea, pulmonary function, exercise tolerance and life quality of both groups were assessed respectively before and after the intervention. Results There were no significant differences in dyspnea symptoms, lung function, exercise endurance, quality of life between two groups before intervention (P>0.05). The dyspnea scored 1.43±0.87 after intervention in the experimental group, and 1.93 ±0.97 in the control group, there was significant difference (Z=-2.293, P=0.022). The 6 min walking test distance was (371.34 ± 67.74) m after intervention in the experimental group, and (301.57 ± 61.67) m in the control group, there was significant difference(t = 4.988, P =0.000). The St. George′s Respiratory Questionnaire (respiratory symptoms, limited activity, influence disease) score and total score were 54.73 ± 11.96, 52.55 ± 14.48, 55.45 ± 10.01, 54.56 ± 10.79 after intervention in experimental group respectively, and 61.19 ± 10.72, 61.35 ± 14.66, 60.48 ± 9.39, 60.93 ± 10.16 in the control group, there were significant differences(t=-2.815--2.397, P<0.05). There was no significant difference in lung function after intervention between two groups (P>0.05). Conclusions The program of shrinking lips abdominal breathing combined with vertical breathing gymnastics can relieve dyspnea in patients with moderate to severe COPD, improve exercise tolerance and quality of life, which is a safe and effective rehabilitation for patients with COPD.

Objective To observe the rotation of subendocardium and subepidium by two-dimensional speckle tracking imaging(2D-STI),and to evaluate its performance in diastolic heart failure patients(DHF)with a normal left ventricular ejection fraction. MethodsNinety-seven consecutive clinically stable patients were enrolled in this study [41 healthy controls,36 with diastolic heart failure,20 with systolic heart failure (SHF)]. High frame rate dynamic two-dimensional images were recorded at the left ventricular short-axis view,including basal, papillary muscle and apical planes. Subendocardial and subepicardial global rotation were measured using Q-lab 7.0 software offline. Results ① In all the subjects, the rotation of the subendocardium was obviously greater than that of subepicardium. ②As seen from the apex,left ventricular subendocardium and subepicardium performed a wringing motion with a clockwise rotation at the base and countclockwise rotation at the apex. ③In the apical plane, subendocardial rotation was significantly lower in both heart failure groups than in controls,and was depressed to a larger extent in SHF patients than in those with DHF. Subepicardial rotation was no significant difference between the DHF group and the control group, though it was significantly lower in patients with SHF. ④At the base, the rotation of subendocardium and subepicardium were not different between DHF and control groups, but it was significantly reduced in patients with SHF. Conclusions The subendocardial rotation is reduced, but subepicardial rotation is normal in DHF patients. On the other hand, in patients with SHF, subendocardial and subepicardial rotation are both reduced. The left ventricular systolic properties are impaired in DHF patients.

Objective:To investigate the application effect of situational simulation combined with the Debriefing-GAS method in the teaching of prenatal genetic counseling.Methods:A total of 30 medical students of the five- and eight-year programs in the classes of 2017 and 2018 who received genetic counseling training in The First Affiliated Hospital of Sun Yat-sen University from May 2021 to May 2022 were selected as research subjects, and situational simulation combined with the debriefing-GAS method was used for the teaching of prenatal genetic counseling. Assessment was performed by the teacher to evaluate the change in genetic counseling abilities during the teaching process, and a questionnaire survey was conducted to investigate the degree of satisfaction with teaching among the students. SPSS 26.0 software was used for data analysis; normally distributed continuous data were expressed as mean±standard deviation, non-normally distributed continuous data were expressed as M d(P 25,P75), and categorical data were expressed as frequency and rate; the paired samples t-test was used for comparison of assessment scores before and after teaching. Results:After teaching, there were significant increases in the assessment scores of genetic counseling [(74.5±18.6) points vs. (87.2±14.5) points, t=4.10, P<0.001] and comprehensive abilities such as clinical ability [(35.4±9.6) points vs. (41.1±6.9) points, t=3.72, P=0.001], doctor-patient communication [(17.5±4.6) points vs. (20.8±3.8) points, t=4.34, P<0.001], professional literacy [(11.0±2.5) points vs. (12.5±2.3) points, t=2.89, P=0.007], teamwork [(3.5±1.0) points vs. (4.2±0.8) points, t=3.67, P=0.001], and organizational effectiveness [(7.1±2.0) points vs. (8.3±1.7) points, t=2.94, P=0.006]. The questionnaire survey showed that the degree of satisfaction among students was rated above satisfaction for the reasonability of the implementation process and links of genetic counseling teaching [3.0 (3.0, 4.0) points], teaching quality [3.5 (3.0, 4.0) points], whether the teaching model could effectively increase the interest and initiative in learning [4.0 (3.0, 4.0) points], the improvement in theoretical knowledge [4.0 (3.0, 4.0) points], communication skills in genetic counseling [3.0 (3.0, 4.0) points], and the understanding of related techniques and application prospect [3.0 (3.0, 4.0) points]. However, two students (6.7%) thought that this teaching model could not efficiently reach teaching objectives, since the teaching process was slightly complicated. Conclusions:Situational simulation combined with the debriefing-GAS method has achieved a good effect in the teaching of prenatal genetic counseling and can help undergraduates to master the theoretical knowledge of prenatal genetic counseling and improve their comprehensive clinical abilities, with a relatively high degree of satisfaction, and therefore, it holds promise for clinical application.

Objective:To analyze clinical characteristics of primary pancreatic lymphoma (PPL) patients.Methods:Clinical features of 22 patients diagnosed as PPL admitted to Peking Union Medical College Hospital from January 2002 to May 2023 were analyzed retrospectively.Results:The median age was 56.4±13.3 years. The median time from onset to diagnosis was 1.0 (1.0, 3.0) months. The main clinical manifestations were abdominal pain (15/22), weight loss (14/22) and jaundice (10/22). Elevated lactate dehydrogenase (LDH) was observed in 15/20 (75%) patients. Only 2 (2/9, 22.2%) patients had increased CA199 levels and 2 (2/9, 22.2%) patients had increased CEA levels. The maximum tumor diameter was 5.0 (3.8, 6.9) cm. Contrast-enhanced CT mostly showed low enhancement lesions. Major pancreatic duct dilatation were rare on CT scan (4/20). Fifteen patients were confirmed by pancreatic pathology, of which 8 were obtained by surgery, 4 were obtained by CT or ultrasound-guided percutaneous biopsy, and 3 were obtained by EUS-FNA. The main pathological type was diffuse large B-cell lymphoma (14/22). 19 patients received chemotherapy, and 6 patients died with a median follow-up of 5.0 (1.5, 35.5) months.Conclusions:PPL is rare and easy to be misdiagnosed. Elevated LDH levels, normal tumor markers, and non-dilatation of main pancreatic duct are important diagnostic clues. It is important to obtain pathology by EUS-FNA and other methods for definite diagnosis.

【Objective】 To investigate the efficacy and safety of sitagliptin combined with metformin versus glimepiride combined with metformin in newly diagnosed type 2 diabetes patients with severe hyperglycaemia. 【Methods】 A randomized controlled and non-inferiority trial was carried out. A total of 129 newly diagnosed type 2 diabetes patients with severe hyperglycaemia [FPG≥200 mg/mL (11.1 mmol/L) and HbA1c≥9.0%] were enrolled and numerally randomly assigned to two groups. The patients received sitagliptin combined with metformin (n=66) or glimepiride combined with metformin (n=63) for 4 weeks and then metformin alone for another 8 weeks. Glycaemic control, weight changes and β-cell insulin secretory capacity were investigated to demonstrate the efficacy and safety of these two treatments. 【Results】 Mean HbA1c reduction was 4.03% in sitagliptin group and 4.13% in glimepiride group after 3 months of treatment. The lower boundary of the two-sided 95% confidence intervals of the mean HbA1c reduction difference between the two groups was -0.648%, which was more than -0.65%, suggesting that the predefined statistical criterion for non-inferiority was achieved. FPG decreased significantly after one month of intervention in both groups (P<0.05). Significant reduction in the time of reaching euglycemia, FPG and weight decrease was observed in sitagliptin group than glimepiride group (P<0.05). The FPG control rate FPG<110 mg/mL (6.1 mmol/L) was higher in sitagliptin group than in glimepiride group (P<0.05). After the 3-month follow-up, FPG, HbA1c and incidence of hypoglycemia showed no significant differences in the two groups, while weight loss and BMI changes showed significant differences in sitagliptin group compared with glimepiride group (P<0.05). No significant differences in β-cell insulin secretory indexes were observed in the two therapy groups (P>0.05). 【Conclusion】 Our study provided evidence that sitagliptin combined with metformin in newly diagnosed diabetes patients with severe hyperglycaemia showed better outcomes in glycaemic remission compared with glimepiride for those who refused insulin injection.

OBJECTIVE To prep are Legumain enzyme and mitochondrial double-stage targeted harmine （HM） liposome （KA@HM-LPS）and preliminary evaluate its pharmaceutical properties ，in vitro antitumor effect and biocompatibility. METHODS Firstly，the preparation and homogenization methods of KA@HM-LPS was screened ，and prepared liposomes were characterized. Secondly，the serum stability ，in vitro release rate ，hemolysis percentage of KA@HM-LPS and cell survival rate under KA@BLPS were determines respectively. Finally ，the cell surivival rate ，mitochondrial targeting and inhibitory effects on cell migration and invasion of KA@HM-LPS were determined. RESULTS KA@HM-LPS was prepared by the thin-film dispersion method ，with encapsulation efficiency of （90.50 ± 0.62）％ . The extrusion moulding method was selected as homogenization method of KA@HM-LPS. The particle size ，polydispersity index ，and Zeta potential of KA@HM-LPS were （211.40±11.67）nm，0.316± 0.014 and（－14.20±0.49）mV，respectively. In 37 ℃，10％ FBS，the particle size of KA@HM-LPS kept stable after 12 h. In vitro release curve of KA@HM-LPS in 20％ plasma conformed to Weibull distribution and had the property of sustained release. When HM concentration was 160 μg/mL，the hemolysis percentage of KA@HM-LPS was （4.23±0.19）％，which was much lower than that of free HM ，with safety. When the mass concentration of KA@BLPS reaches 400 μg/mL，the survival rate of LO 2 cells was （94.40 ± 6.12）％ ，and the biocompatibility was good. Cell test results in vitro showed that ，inhibitory effect of KA@HM-LPS on liver cancer cells with overexpression of Legumain enzyme （LGMN -SK-Hep-1） was significantly higher than that of normal liver cancer cells SK-Hep- 1； compared with SK-Hep-1，LGMN +-SK-Hep-1 cells had a higher uptake efficiency of the liposome ；KA@HM-LPS could significantly inhibit the migration and invasion of LGMN +- SK-Hep-1 cells. CONCLUSIONS KA@HM-LPS is prepared successfully ，which can effectively inhibit the migration and invasion of liver cancer cells with Legumain enzyme overexpression ，and improve the blood compatibility of HM.

Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1