At present, some "5+3" integration students have different levels of understanding and application problems in various stages, such as role transformation, professional knowledge and technology, communication ability and humanistic care ability, clinical thinking and evidence-based medicine concepts, clinical research thinking, learning and work attitude. This research will permeate and run through the training of "5+3" integrated students' diagnostic and therapeutic operation ability through the training of modern clinical thinking oriented by post competency, and integrate humanistic care, evidence-based medicine, learning attitude, working attitude, and attitude towards patients in the whole process to gradually complete the comprehensive training goal of clinical thinking oriented by post competency + diagnostic and therapeutic operation ability.

Objective To investigate the differences in chemical components and bacterial diversity on the surface of Citrus reticulata at various drying temperatures(35、45、55、65℃).Methods At various drying temperatures,Citrus reticulata from Dahongpao produced in Chongqing Wanzhou was dried.By using HPLC,the effects of various drying temperatures on the hesperidin,hesperidin,and kaempferin concentrations in Citrus reticulata were examined.By using GC-MS,the effects of various drying temperatures on the Citrus reticulata volatile components were examined.The differences in bacterial population structure on the surface of Citrus reticulata at various drying temperatures were examined using high throughput sequencing.Results The higher the temperature,the quicker Citrus reticulata will dry.The amount of hesperidin and hesperidin in Citrus reticulata was not significantly affected by different drying temperatures.The amount of Citrus reticulata increased as the drying temperature rose.GC-MS analysis identified 15 main components in Citrus reticulata,and the proportion of some volatile aroma components decreased with the increase of drying temperature;Such as laurylene,linalool,carvol α-Orange aldehyde,etc.With the increase of drying temperature,the dominant bacteria of Proteobacteria has an upward trend.At the same time,the dominant bacteria of Halomonas and Porphyromonas have changed to Metallobacterium.Conclusion If the drying temperature is too high,the volatile components in the dried Citrus reticulata may be transformed or destroyed due to the instability of heating.The difference of the bacterial flora on the surface of Citrus reticulata at different drying temperatures may cause the change of the volatile components in the later aging process.Considering the quality of dried tangerine peel,low temperature and hot air drying is the better drying method.

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

Objective:To explore the prolonged therapeutic regimen for patients with plaque psoriasis, who showed a positive response to 4-week treatment with tazarotene/betamethasone dipropionate cream, but were not completely cured.Methods:A multicenter, randomized, open-labelled, parallel-controlled clinical study was conducted. A total of 232 patients with plaque psoriasis were collected, who showed a positive response to previous 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured with the psoriasis area and severity index[PASI] improvement rate being 50%-90%. At week 5, they were randomly and equally divided into 2 groups: test group receiving treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream once a day, and control group receiving a sequential regimen of 0.05% tazarotene gel on weekdays once a day followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream on weekends once a day. After 2-and 4-week prolonged treatment, the efficacy and safety of the 2 therapeutic regimens were evaluated and compared. Measurement data were compared between 2 groups by using covariance analysis or t test, and enumeration data were compared by using chi-square test. Results:From the 5th to the 8th week, 200 out of the 232 patients completed the treatment. Data collected from 110 patients in the test group and 112 in the control group were enrolled into the full analysis set, and those from both 113 patients in the test group and control group were enrolled into safety analysis set. After consecutive 6-and 8-week treatment, the decline rates of the PASI score were 73.05% ± 16.69% and 78.46% ± 15.40% respectively in the test group, which were significantly higher than those in the control group (66.73% ± 21.77%, 67.02% ± 34.19%, respectively, both P < 0.05) . After 6-week treatment, the proportion of subjects who achieved PASI90 was significantly higher in the test group (14 cases, 12.7%) than in the control group (5 cases, 4.5%, χ2=4.842, P=0.028) ; After 8-week treatment, the proportions of subjects who achieved PASI75 and PASI90 (61.8%, 23.6%, respectively) were significantly higher in the test group than in the control group (48.2%, 12.5%, respectively, both P < 0.05) . During the consecutive 8-week treatment, there was no significant difference in the incidence rate of adverse reactions between the test group (15.0%) and control group (23.9%, χ2=2.822, P=0.093) . Conclusion:For patients who showed a positive response to 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured, the continuous use of 0.05%/0.05% tazarotene/betamethasone dipropionate cream for 4 weeks is a superior therapeutic regimen compared with the sequential regimen of 0.05% tazarotene gel followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream.

The first-line nucleos(t)ide analogs (NAs) based antiviral drugs can effectively inhibit HBV replication and slow down the progression of chronic hepatitis B. However, about 20% of patients receiving standard NAs antiviral therapy will still develop low-level viremia (LLV). Therefore, understanding the occurrence mechanism of LLV will help to optimize antiviral treatment regimens and improve the prognosis of patients with chronic hepatitis B. This article systematically summarizes the possible mechanisms of LLV occurrence, and the important factor of NAs failure. Taking into account the unique limitations of NAs competitive inhibition of virus replication, weakening host's immune response is not enough to directly eliminate infected hepatocytes. This makes it difficult to achieve a complete virological response in some patients with the active compensatory proliferation of residual infected hepatocytes and the accompanying effective removal or dilution of covalent, closed, circular DNA (cccDNA) pools. Therefore, it is speculated that activating host immunity can eliminate infected liver cells and may be more conducive to address LLV.

Objective:To explore the feasibility of direct renin inhibitor aliskiren for the treatment of severe or critical coronavirus disease 2019 (COVID-19) patients with hypertension.Methods:The antihypertensive effects and safety of aliskiren was retrospectively analyzed in three severe and one critical COVID-19 patients with hypertension.Results:Four patients, two males and two females, with an average age of 78 years (66-87 years), were referred to hospital mainly because of respiratory symptoms. Three were diagnosed by positive novel coronavirus 2019 (2019-nCoV) nucleic acid or antibody, and the critical patient with cardiac insufficiency was clinically determined. Two patients were treated with calcium channel antagonist (CCB), one with angiotensin converting enzyme inhibitor (ACEI), and one with angiotensin Ⅱ receptor antagonist (ARB). After admission, ACEI and ARB were discontinued, one patient with heart failure was treated by aliskiren combined with diuretic.Three patients were treated with aliskiren combined with CCB among whom two withdrew CCB due to low blood pressure after 1 to 2 weeks. Based on comprehensive treatment including antiviral and oxygenation treatment, blood pressure was satisfactorily controlled by aliskiren after three to four weeks without serious adverse events. All patients were finally discharged.Conclusion:Our preliminary clinical data shows that antihypertensive effect of aliskiren is satisfactory and safe for severe COVID-19 patients complicated with hypertension.

Objective To observe the benefits and safety of different maintenance doses of azithromycin for long-term treatment in adult patients with non-cystic fibrosis (CF) bronchiectasis. Methods One hundred and thirty-two indigenous outpatients (>18 years old) with stable non-CF bronchiectasis were enrolled. All patients were randomly assigned to a control group and two treatment groups. Patients in the azithromycin fixed-dose treatment group received oral azithromycin (250 mg daily) and ambroxol hydrochloride (30 mg, 3 times/d). Azithromycin progressively decreased dosage treatment group received oral azithromycin (250 mg daily for 8 weeks-250 mg 3 times/week for 8 weeks-250 mg 2 times/week for 10 weeks) and ambroxol hydrochloride (30 mg, 3 times/d). Subjects in control group only received ambroxol hydrochloride therapy. The course of treatment lasted for 26 weeks. Spirometry, exacerbations, sputum microbiology, quality of life, dyspnea scores and adverse effects were monitored after treatment for 26 weeks. Results One hundred and twenty-nine evaluable subjects completed the study. After treatment, the level of percentage of estimated value forced expiratory volume in 1 second (FEV1% Pred) in azithromycin fixed-dose treatment group and azithromycin progressively decreased dosage treatment group was significantly higher than that before treatment: (83.01 ± 5.79)% vs. (79.39 ± 3.53)%, (84.97 ± 5.10)% vs. (80.94 ± 3.46)%, P<0.05. Forced expiratory flow between 25% and 75% of vital capacity (FEF25%- 75%) was also increased in two groups: (54.87 ± 5.72) % vs. (51.86 ± 8.16)%, (55.65 ± 3.39)% vs. (53.46 ± 5.75)% , there was significant difference (P<0.05). But the levels of above parameters between two groups after treatment had no significant differences (P >0.05). The parameters of FEV1% Pred, forced expiratory volume in 1 second (FEV1)/forced ventilatory capacity (FVC) and FEF25%-75%were lower compared to those before treatment in the control group (P <0.05). However, the scores of LRTI-VAS and FACED in control group after treatment were decreased slightly: (20.55 ± 1.76) scores vs. (21.34 ± 1.86) scores, P<0.05; (4.16 ± 0.75) scores vs. (4.36 ± 0.72) scores, P > 0.05. Seven episodes of acute exacerbation was occured during 26 weeks, 2 cases exited. The others did not interrupt azithromycin treatment during acute exacerbation. Drug-related adverse reactions were mild. Conclusions For adult stable patients with non-CF bronchiectasis, the clinical symptoms and airflow limitation are improved after long-term treatment of low-dose azithromycin. Similar effects on FACED score and LRTI-VAS score are observed in patients with progressively decreased dosage of azithomycin.

Objective To understand the changes of schistosomiasis epidemic situation,so as to provide the evidence for for?mulating schistosomiasis control strategy in the Hexi reservoir area. Methods From 2012 to 2015,Xinyuan Village,Meishan Town in the north entrance of Hexi reservoir was selected as a monitoring site. According to the requirements of the monitoring program of schistosomiasis surveillance in Zhejiang Province,the Schistosoma japonicum infection was investigated by using the serological screening(IHA),and the basic situation of the surveillance site was also investigated. Results From 2012 to 2015,167 environments(21.68 hm2)were surveyed,and 2 slices(0.1 hm2)were found with Oncomelania hupensis snails. The detection rate of frames with snails was 0.12%,and the living snail density was 0.0192 snails per 0.1 m2. Totally 374 snails were dissected and no schistosome infected snails were found. A total of 970 local residents and 8 748 mobile people were investigated with the serological tests,and no schistosome infected people were found. In addition,3 085 cattle were investigated and no in?fected ones were found. Conclusion The schistosomiasis epidemic situation is stable in the Hexi reservoir area,but we still should strengthen the monitoring of imported source of infection and snail status,and increase the efforts of environmental trans?formation.

objective To understand the status of Oncomelania hupensis snail distribution and diffusion in main drainages of Hexi Reservoir and evaluate the snail control effect of the schistosomiasis control engineering of Hexi Reservoir. Methods The O. hupensis snails were investigated by using the straw curtain method and fishing net method in different areas of the main drainages of Hexi Reservoir and the results were analyzed. Results A total of 1 800 straw curtains were used and 37 snails were found in Naxi stream. Totally 5 870 kg floats were salved and no snails were found. Conclusion The schistosomiasis con?trol engineering of Hexi Reservoir is effective in the prevention of the snail diffusion but there are still snails in the upstream. Therefore the snail surveillance and control need to be strengthened.

Objective To evaluate the effect of schistosomiasis control projects in Hexi Reservoir on Oncomelania hupensis snail control. Methods The canal hardening+main water system widening+the overflow dam project,the concrete slope protec-tion,the banking and reclamation + concrete slope protection project,the environment reform project,and the comprehensive treatment were implemented in the tail area,the hydro-fluctuation belt,the rainwater harvesting zoon of the upstream area,the dam area,and the downstream area of the reservoir,respectively. The changes of the snail situation were investigated before and after the construction of the reservoir,and the snail control effects of the schistosomiasis control projects in different parts of the reservoir were analyzed. Results There were no Oncomelania snails found 3 years in the bottom area,dam area,hydro-fluctua-tion belt,tail region and downstream of the dam after the construction and storage of the reservoir and the implementation of the schistosomiasis control projects. In the rainwater harvesting zoon of the upstream area,the density of living snails decreased from 0.620 4 snails/0.1 m2 in 2009 to 0.113 2 snails/0.1 m2 in 2013,but the snail area still remained. Conclusions The schistosomia-sis control projects in Hexi Reservoir have effectively prevented the diffusion of Oncomelania snails from the rainwater harvesting zone of the upstream area to the dam area,and they are effective in the snail control.