OBJECTIVE To introduce a case of interstitial pneumonia induced by vedolizumab （VDZ）， summarize and analyze the characteristics of the occurrence of VDZ-associated lung toxicity， and provide a reference for the clinically safe use of drugs. METHODS From the perspective of clinical pharmacists， the diagnosis and treatment of a case of VDZ-induced interstitial pneumonia were retrospectively analyzed， and the association of adverse drug reactions （ADR） was analyzed. Retrieving from Chinese and English databases such as CNKI， VIP， PubMed and Web of Science， case reports of VDZ-associated lung toxicity were summarized and analyzed. RESULTS The patient developed interstitial pneumonia during the use of VDZ and empirical anti- infective therapy with antibiotics was ineffective. After withdrawal of VDZ and treatment with methylprednisolone， symptoms and imaging examinations improved， but interstitial pneumonia still existed. According to Naranjo’s ADR evaluation scale and based on China Adverse Drug Reaction Reporting and Monitoring Manual， the association between VDZ and interstitial pneumonia was “very likely”. Results of the literature analysis showed that among 29 involved patients （including the patient reported in this article）， there were 19 males and 10 females， with an average age of （49.24±17.06） years. Lung toxicity mainly included VDZ- associated pneumonia， eosinophilic pneumonia， pulmonary granulomas or necrobiotic nodules， interstitial lung injury， etc.， which mostly occurred ≤24 weeks after medication （58.62%）. The main clinical manifestations included cough， dyspnea and fever. The vast majority of patients improved or recovered after drug withdrawal and/or glucocorticoid treatment， but one patient died of respiratory failure. CONCLUSIONS Lung toxicity is a rare ADR of VDZ with insidious onset and nonspecific symptoms. Once patients experience symptoms such as cough and dyspnea， early diagnosis，timely drug withdrawal，and symptomatic treatment measures such as glucocorticoid should be taken to ensure medication safety.

In order to improve the teaching quality of engineering courses, we introduced a multi-dimensional teaching method into the teaching reform of biology majors in colleges based on the portfolio assessment in the curriculum of Cell Engineering. We reformed the knowledge system, teaching form and implementation scheme of this course. By combining the reform of online teaching, interactive teaching, case teaching and other teaching modes, the students mastered the relevant professional knowledge and the scientific and technological frontier of Cell Engineering. Moreover, their learning interest and enthusiasm, ability of analyzing and solving professional problems related to Cell Engineering also improved. The implementation of teaching reform of this course provides a reference for other similar professional courses in colleges.
Humans ; Curriculum ; Students ; Learning ; Cell Engineering

A 64-year-old male patient with gastric adenocarcinoma received chemotherapy with oxaliplatin (250 mg intravenous infusion on day 1) and tegafur gimeracil oteracil potassium (60 mg orally twice daily on day 1 to day 14, 21 days as a cycle). One month later, he was given nivolumab immunotherapy (240 mg intravenous infusion on day 1, 14 days as a cycle). On the 2nd day of the 4th cycle of nivolumab treatment (the 44th day after the first dose), the patient developed diarrhea with watery stools, 3 to 4 times a day, accompanied by mild abdominal pain; 3 days later, the diarrhea worsened, showing dark red bloody stools, covered with pus moss, up to 10 times a day, accompanied by obvious abdominal pain. According to colonoscopy and histological examination results, ulcerative colitis (initial onset, total colon, active stage, and severe) was diagnosed, which was considered as a grade 3 immune-related colitis induced by nivolumab. After suspension of chemotherapy and immunotherapy, and administration of glucocorticoids and octreotide, the patient′s abdominal pain and diarrhea were gradually improved. On the 45th day of nivolumab withdrawal, the patient received chemotherapy with oxaliplatin and tegafur gimeracil oteracil potassium again, and colitis did not recur.

Objective:To investigate the relationship between NOD-like receptors 3 (NLRP3) inflammasomes mediated inflammatory response and the pathogenesis of depression, and to investigate the effect of fluoxetine on this process.Methods:120 male C57BL/6J (wild-type) mice were randomly divided into control group 1, control group 2, chronic unpredictable mild stress (CUMS) group, and CUMS plus fluoxetine group. Another 30 male C57BL/6J (NLRP3-/-) mice were selected as NLRP3-/- group. Control group 1 and control group 2 had No treatment; CUMS group, CUMS plus fluoxetine group, and NLRP3-/- group were given chronic unpredictable mild stimulation for six weeks. After modeling, mice in control group 2 and CUMS plus fluoxetine group were intraperitoneally injected with fluoxetine (10 mg/(kg·d)). In contrast, mice in the other three groups were injected with the same amount of normal saline every day for four weeks. Behavioral tests were performed once a week before and after stress stimulation. Tail venous blood was drawn immediately before stress stimulation, three weeks later and six weeks after stress stimulation and was centrifuged at 3000 r/min for 10 min. The supernatant was kept and frozen for future use. Serum levels of interleukin-1β(IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked immunosorbent assay. After drug intervention (10 mg/(kg·d) fluoxetine or the same volume of normal saline), the mice in each group underwent behavioral tests once a week. The results included the sugar water preference test, forced swimming test (FST), and tail suspension test (TST). Tail venous blood was drawn from mice in each group at 1, 3, and 4 weeks after fluoxetine administration, and the supernatant was centrifuged and stored for later use. Serum levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay. At the above time points, 5 mice in each group were sacrificed each time, and fresh hippocampal tissues were collected and stored at a low temperature. NLRP3, urinary winter peptidase (caspase-1), the induction of transcription factors-KB (nuclear factor-κB, NF-κB), IL-1β and the IL-18 in the hippocampus brain regions were detected by using Western Blot.Results:(1) Model establishment: After six weeks of CUMS, compared with control group 1 and control group 2, the sugar water consumption of mice in CUMS group and CUMS+fluoxetine group was significantly reduced, and the immobility time of FST and TST was significantly prolonged, which proved that the model establishment was successful. After CUMS, NLRP3-/- group mice did not show depression-like changes in FST, sugar water preference test, and TST, which indicated that the model failed to be established. (2) After intraperitoneal fluoxetine injection, there were no significant differences in sugar water consumption, FST and TST immobility time between control group 2 and control group 1 ( P>0.05), and the sugar water consumption of mice in CUMS plus fluoxetine group was significantly increased, compared with CUMS group ( P<0.05). The immobility time of FST and TST was significantly shortened ( P<0.05). (3) The results of the enzyme-linked immunosorbent assay showed that after stimulation of CUMS, compared with control group 1 and control group 2, the serum levels of IL-1β and IL-18 in CUMS group and CUMS plus fluoxetine group were significantly increased ( P<0.05), while NLRP3-/- group had no significant change ( P>0.05). After fluoxetine administration, the serum levels of IL-1β and IL-18 in CUMS plus fluoxetine group were significantly lower than those in CUMS group ( P<0.05). (4) Western blotting results showed that after stimulation of CUMS, compared with control group 1 and control group 2, mice brain hippocampus NLRP3 expression, caspase-1 activation and induction of transcription factors-κB (nuclear factor-κB, NF-κB), IL-1β, IL-18 expression significantly increased ( P<0.05) in CUMS and CUMS plus fluoxetine group. After fluoxetine treatment, mice brain hippocampus NLRP3 expression, caspase-1 activation, NF-κB, IL-1β, and IL-18 expression in CUMS plus fluoxetine group had a significant reduction (restored to control 1 group by 99%, 91%, 97%, 95%, and 97% respectively). Conclusion:(1) CUMS may bring more NLRP3, caspase-1, NF-κB, IL-1β, and IL-18 expression in mice hippocampus, which cannot be seen, in the NLRP3 gene knockout mice; (2) The fluoxetine treatment may significantly decrease the NLRP3, caspase-1, NF-κB, IL-1β, IL-18 expression on depressive model mice, and improve depressive behavior.

A 64-year-old male patient with gastric adenocarcinoma received chemotherapy with oxaliplatin (250 mg intravenous infusion on day 1) and tegafur gimeracil oteracil potassium (60 mg orally twice daily on day 1 to day 14, 21 days as a cycle). One month later, he was given nivolumab immunotherapy (240 mg intravenous infusion on day 1, 14 days as a cycle). On the 2nd day of the 4th cycle of nivolumab treatment (the 44th day after the first dose), the patient developed diarrhea with watery stools, 3 to 4 times a day, accompanied by mild abdominal pain; 3 days later, the diarrhea worsened, showing dark red bloody stools, covered with pus moss, up to 10 times a day, accompanied by obvious abdominal pain. According to colonoscopy and histological examination results, ulcerative colitis (initial onset, total colon, active stage, and severe) was diagnosed, which was considered as a grade 3 immune-related colitis induced by nivolumab. After suspension of chemotherapy and immunotherapy, and administration of glucocorticoids and octreotide, the patient′s abdominal pain and diarrhea were gradually improved. On the 45th day of nivolumab withdrawal, the patient received chemotherapy with oxaliplatin and tegafur gimeracil oteracil potassium again, and colitis did not recur.

Objective:To investigate the relationship between NOD-like receptors 3 (NLRP3) inflammasomes mediated inflammatory response and the pathogenesis of depression, and to investigate the effect of fluoxetine on this process.Methods:120 male C57BL/6J (wild-type) mice were randomly divided into control group 1, control group 2, chronic unpredictable mild stress (CUMS) group, and CUMS plus fluoxetine group. Another 30 male C57BL/6J (NLRP3-/-) mice were selected as NLRP3-/- group. Control group 1 and control group 2 had No treatment; CUMS group, CUMS plus fluoxetine group, and NLRP3-/- group were given chronic unpredictable mild stimulation for six weeks. After modeling, mice in control group 2 and CUMS plus fluoxetine group were intraperitoneally injected with fluoxetine (10 mg/(kg·d)). In contrast, mice in the other three groups were injected with the same amount of normal saline every day for four weeks. Behavioral tests were performed once a week before and after stress stimulation. Tail venous blood was drawn immediately before stress stimulation, three weeks later and six weeks after stress stimulation and was centrifuged at 3000 r/min for 10 min. The supernatant was kept and frozen for future use. Serum levels of interleukin-1β(IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked immunosorbent assay. After drug intervention (10 mg/(kg·d) fluoxetine or the same volume of normal saline), the mice in each group underwent behavioral tests once a week. The results included the sugar water preference test, forced swimming test (FST), and tail suspension test (TST). Tail venous blood was drawn from mice in each group at 1, 3, and 4 weeks after fluoxetine administration, and the supernatant was centrifuged and stored for later use. Serum levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay. At the above time points, 5 mice in each group were sacrificed each time, and fresh hippocampal tissues were collected and stored at a low temperature. NLRP3, urinary winter peptidase (caspase-1), the induction of transcription factors-KB (nuclear factor-κB, NF-κB), IL-1β and the IL-18 in the hippocampus brain regions were detected by using Western Blot.Results:(1) Model establishment: After six weeks of CUMS, compared with control group 1 and control group 2, the sugar water consumption of mice in CUMS group and CUMS+fluoxetine group was significantly reduced, and the immobility time of FST and TST was significantly prolonged, which proved that the model establishment was successful. After CUMS, NLRP3-/- group mice did not show depression-like changes in FST, sugar water preference test, and TST, which indicated that the model failed to be established. (2) After intraperitoneal fluoxetine injection, there were no significant differences in sugar water consumption, FST and TST immobility time between control group 2 and control group 1 ( P>0.05), and the sugar water consumption of mice in CUMS plus fluoxetine group was significantly increased, compared with CUMS group ( P<0.05). The immobility time of FST and TST was significantly shortened ( P<0.05). (3) The results of the enzyme-linked immunosorbent assay showed that after stimulation of CUMS, compared with control group 1 and control group 2, the serum levels of IL-1β and IL-18 in CUMS group and CUMS plus fluoxetine group were significantly increased ( P<0.05), while NLRP3-/- group had no significant change ( P>0.05). After fluoxetine administration, the serum levels of IL-1β and IL-18 in CUMS plus fluoxetine group were significantly lower than those in CUMS group ( P<0.05). (4) Western blotting results showed that after stimulation of CUMS, compared with control group 1 and control group 2, mice brain hippocampus NLRP3 expression, caspase-1 activation and induction of transcription factors-κB (nuclear factor-κB, NF-κB), IL-1β, IL-18 expression significantly increased ( P<0.05) in CUMS and CUMS plus fluoxetine group. After fluoxetine treatment, mice brain hippocampus NLRP3 expression, caspase-1 activation, NF-κB, IL-1β, and IL-18 expression in CUMS plus fluoxetine group had a significant reduction (restored to control 1 group by 99%, 91%, 97%, 95%, and 97% respectively). Conclusion:(1) CUMS may bring more NLRP3, caspase-1, NF-κB, IL-1β, and IL-18 expression in mice hippocampus, which cannot be seen, in the NLRP3 gene knockout mice; (2) The fluoxetine treatment may significantly decrease the NLRP3, caspase-1, NF-κB, IL-1β, IL-18 expression on depressive model mice, and improve depressive behavior.

We introduce the portfolio assessment into the classroom teaching reform in the curriculum of Cell Engineering, a specialty course in bioengineering & biotechnology. We established a complete classroom evaluation system that was divided the classroom assessment system of portfolio into four stages including the preparation stage, training stage, implementation stage and exhibition stage. We also discuss the feasibility and necessity of implementing the portfolio evaluation method in the course of cell engineering, the construction of evaluation system, and the key points and matters needing attention in the implementation process. The classroom reform is very productive, not only the classroom atmosphere has been activated, students' learning initiative and autonomy has been enhanced, but also the students' ability to analyze and solve professional problems related to cell engineering technology has been improved. The implementation of classroom teaching reform of this course can provide reference for other similar professional courses in colleges and universities.
Cell Engineering ; Curriculum ; Humans ; Learning ; Students ; Universities

Objective:To evaluate the expression of LEF1 protein in lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and small B-cell lymphomas, and its value in pathologic diagnosis and differential diagnosis of LBL/ALL.Methods:53 cases of LBL/ALL were collected at shanghai Tongji Hospital from January 2012 to December 2019. The protein expression of LEF1 and TdT was detected by immunohistochemistry in 53 paraffin-embedded tissue samples of LBL/ALL. The specificity and sensitivity of LEF1 and TdT in the diagnosis of LBL/ALL were compared. The expression of LEF1 protein in 77 cases of small B-cell lymphomas including chronic lymphocytic leukemia/small lymphoid lymphoma (CLL/SLL), follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and Waldenstrom′s macroglobulinemia/lymphoplasmacytic lymphoma was studied. The correlation between LEF1 expression and overall survival (OS) and progression-free survival (PFS) was performed by univariate analysis.Results:The expression of LEF1 in LBL/ALL was 100% (53/53), the median value was 90%; the expression of TdT was 84.9% (T-LBL/ALL 78.1%, B-LBL/ALL 95.2%), the median value was 80%; the expression rate and median value of LEF1 and TdT were significantly different ( P=0.008 and 0.001 respectively). The expression of LEF1 in CLL/SLL was 14/18, the median value was 45%; LEF1 was not expressed in follicular lymphoma (0/16), mantle cell lymphoma (0/16), marginal zone lymphoma (0/19), and Waldenstrom′s macroglobulinemia/lymphoplasmacytic lymphoma (0/8). LEF1 expression was significantly different between B-LBL/ALL and small B-cell lymphomas. The median follow-up time of LBL/ALL cases in this group was 16 months. There was no statistical difference between LEF1 expression and the OS and PFS in LBL/ALL patients. Conclusions:Immunohistochemical staining of LEF1 has high sensitivity and good specificity in the diagnosis of LBL/ALL, and its combination with TdT can improve the diagnostic rate of LBL/ALL.

Objeetive : The epidemiological characteristics of confirmed cases of the 2019 novel coronavirus diseases (COVID-19) which was reported in Wenzhou by February 28,2020 were described and analyzed to provide evidence for prevention and control measures in next stage. Methods: The field investigation method was employed on all suspected and confirmed cases. The data of time,spatial and population distribution, source of infection and detective routes of all confirmed cases of COVID-19 in Wenzhou were collected and extracted from the reports of field investigation and the National Diseases Prevention and Control Information System. Results: As of February 20,2020,504 confirmed cases of COVID-19 were diagnosed in Wenzhou, which included one death case. Among all 13 counties, the highest number of confirmed cases were distributed in Yueqing,Ruian and Lucheng. Among 504 cases, the male to female ratio was reported as 1.14:1. The youngest case was 2 years old while the oldest case was 93 years old. Most of the confirmed cases were among people between the ages of 25 and 64 years old. The most common occupation of the confirmed cases was businessman,which accounts for 29.76% (150 cases). Clinical symptoms of the first confirmed case of COVID-19 in Wenzhou occurred on January 4, 2020. Approximately 70% of cases had the first symptoms from January 19 to February 1. The daily number of new cases on January 24 and January 26 were the highest while the number of new cases per day declined significantly after February 2, and there were no new cases after February 14. Among all confirmed cases, the infection source of 61.71% cases were related to Wuhan. As of February 20, 2020, a total of 79 clusters were reported in Wenzhou, which involved 330 cases. Approximately 30% of confirmed cases came to hospitals unaccompanied by community staffs, and cases which confirmed after February 13 were basically found in central isolation locations or by grid checkers. Conclusions The main reason for the high case numbers of COVID-19 in Wenzhou, in Zhejiang province, was the high number of wenzhou citizens who work in Wuhan. Imported cases account for the most confirmed cases during the early period, while mainly confirmed cases were local cases during the middle and late periods. The outcomes suggest the prevention and control measures employed by Wenzhou government, which included closed-loop control and quantitative control, have achieved remarkable results and the epidemic of COVID-19 in Wenzhou has been initially controlled.

Objective: To conduct an epidemiological investigation on the first reported case of coronavirus disease 2019 （COVID-19） in Zhejiang Province, so as to provide reference for prevention and control of the disease. Methods : According to the COVID-19 Diagnosis and Treatment Program （Trial） and the COVID-19 Prevention and Control Program （Trial） issued by National Health Commission of China, a field investigation was employed on a case of fever from Wuhan reported by Wenzhou in January 15, 2020; the real-time reverse transcription polymerase chain reaction （RT-PCR） assay was performed to detect the nucleic acid of severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2） from the sputum specimens or throat swabs of the case; the close contacts of the case were tracked down; relevant prevention and control measures were implemented. Results : The case had lived in Wuhan for long. On January 4 of 2020, he felt cold and uncomfortable without obvious inducement, and drove back to Wenzhou with his wife. He had fever （up to 39 ℃）, cough and expectoration on the next day. On January 9, the chest computed tomographic （CT） scan showed bilateral high-density patchy shadowing with blurred edges. On January 16, his throat swab and sputum samples were collected and sent to Zhejiang Provincial Center for Disease Control and Prevention （CDC） for detection of SARS-CoV-2. The result turned out to be positive on January 17, then was rechecked and confirmed by Chinese CDC on January 20. Two weeks before the onset of the disease, the patient was engaged in the door-to-door persuasion of installing elevators in an old residential area of Wuhan, and he denied any connection with other COVID-19 cases,markets,（sick or dead） poultry or poultry products. Totally 26 close contacts were identified and kept in quarantine. During this period,three of them developed fever or respiratory symptoms, but were excluded from COVID-19. On the afternoon of January 16,the health system of Zhejiang Province and Wenzhou City launched an emergency plan and implemented a series of prevention and control measures such as isolation and treatment of cases,screening and isolation of close contacts,and public health education. Conclusion According to the epidemiological history,clinical features and laboratory test Results,the patient was identified as the first reported case of COVID-19 in Zhejiang Province.