1.Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production
Wang-long CHU ; Tong-jing LI ; Yan SHANGGUAN ; Fang-tao HE ; Jian-fu WU ; Xiu-ping ZENG ; Tao GUO ; Qing-fang WANG ; Fen ZHANG ; Zhen-zhong ZHONG ; Xiao LIANG ; Jun-yuan HU ; Mu-yun LIU
Acta Pharmaceutica Sinica 2024;59(3):743-750
Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.
2.Cyberbullying and college students'depression:the role of self-acceptance and dormitory interpersonal relationship
Zheng FANG ; Tingting ZHANG ; Xiu LI
Journal of Shenyang Medical College 2024;26(3):244-247,336
Objective:To explore the influence mechanism of cyberbullying on college students'depression,especially the role of self-acceptance and dormitory interpersonal relationship.Methods:A total of 460 college students were investigated with the Cyberbullying Scale,Self-acceptance Scale,Dormitory Interpersonal Relationship Diagnostic Scale and Self-rating Depression Scale.And 429 valid questionnaires were collected.Results:After controlling for the variable of student cadres,cyberbullying of college students could positively predict depression.Self-acceptance and dormitory interpersonal relationship played a mediating role in the effect of cyberbullying on college students'depression.Self-acceptance and dormitory interpersonal relationship affected the relationship between depression and cyberbullying through chain mediators.Conclusion:College students'cyberbullying can not only directly affect depression,but also indirectly affect depression through the chain mediators of self-acceptance and dormitory interpersonal relationship.
3.Effects of oral probiotics during chemotherapy on gut microbiota and cognitive dysfunction in breast cancer patients
Hong-Min JI ; Xiu-Chuan LI ; Chun-Fang LIU ; Meng-Yuan ZHANG ; Qiong GUO ; Yi LI ; Jun QIAN
Parenteral & Enteral Nutrition 2024;31(2):92-100
Objective:To investigate the effects of oral probiotics on intestinal microbiota and cognitive dysfunction in breast cancer chemotherapy patients. Methods:Thirty breast cancer patients who received anthracycline chemotherapy between December 2021 and June 2022 in the Department of Oncology, the First Affiliated Hospital of Bengbu Medical University were included in this study. The patients were randomly divided into the observation and control groups (15 cases per group). During chemotherapy, the observation group was additionally given oral probiotics. The fecal microbiota compositions before and after chemotherapy were detected using 16S rDNA sequencing. The changes in patients' subjective and objective cognitive function levels were evaluated by Montreal Cognitive Assessment (MoCA) and Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog), respectively. Results:The microbiota diversity, as indicated by the Chao, Ace, Shannon and Simpson indices, showed no significant difference between two groups (P>0.05). As compared with the control group, the relative abundance of the genus Actinomyces in the feces was significantly higher than in the observation group (P<0.05). By contrast, the relative abundance of the genera Acetoanaerobium, Lachnospiracea_incertae_sedis, and unclassified_Frankineae bacteria was significantly lower in the observation group (P<0.05). The total scores of the objective and subjective cognitive function as well as the scores of each dimension in both groups were markedly decreased after chemotherapy (P<0.05). The scores in the observation group were higher than those in the control group after chemotherapy (P<0.05). During chemotherapy, the presence of the gastrointestinal adverse reactions (constipation, nausea and vomiting, diarrhea and abdominal distension) in the observation group were significantly lower than in control group (P<0.05). Conclusion:Oral probiotics could improve the cognitive impairment and reduce the presence of the gastrointestinal side effects in the breast cancer patients receiving chemotherapy, which may be caused by modulating the intestinal microbiota.
4.Research Progress of Biomimetic Imprinting Affinity Analysis Technique
Zhao-Zhou LI ; Yu-Hua WEI ; Xiao-Chong ZHANG ; Xiu-Jin CHEN ; Yao WANG ; Hua-Wei NIU ; Fang LI ; Hong-Li GAO ; Hui-Chun YU ; Yun-Xia YUAN
Chinese Journal of Analytical Chemistry 2024;52(6):763-777
Molecular imprinting is a biomimetic technique that simulates the specific recognition of biological macromolecules such as antibody. Based on molecular imprinting and high-specificity affinity analysis,the biomimetic imprinting affinity analysis (BIA) possesses many advantages such as high sensitivity,strong tolerance,good specificity and low cost,and thus,it has shown excellent prospects in food safety detection,pharmaceutical analysis and environmental pollution monitoring. In this review,the construction methods of recognition interfaces for BIA were summarized,including bulk polymerization,electro-polymerization and surface molecular imprinting. The application of molecularly imprinted polymers in different analysis methods,such as radiolabeled affinity analysis,enzyme-labeled affinity analysis,fluorescence-labeled affinity analysis,chemiluminescence affinity analysis and electrochemical immunosensor was mainly discussed. Furthermore,the challenges and future development trends of BIA in practical application were elucidated. This review might provide new reference ideas and technical supports for the further development of BIA technique.
5.Clinical trial of semaglutide in adults based on the FAERS database
Yi-Ru ZHAO ; Zhen-Wei FANG ; Lin ZHANG ; Xiu-Jin SHI ; Meng-Di ZHANG ; Yang LIN
The Chinese Journal of Clinical Pharmacology 2024;40(2):264-268
Objective We aim to analyse semaglutide related adverse events in real-world,overall and by gender and age subgroups and compare the differences of different gender and age patients in adverse events,in order to supply references for security usage in the clinic.Methods OpenVigil 2.1 was used to search FDA Adverse Event Reporting System for semaglutide related adverse events from the establishment of the databases to April 2023.According to age and gender,patients were divided into 18-64 years old group and≥65 years old group,male group and female group.We selected ten adverse events which we interested(nausea,diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,hypoglycaemia,diabetic retinopathy,acute kidney injury and thyroid cancer/medullary thyroid cancer)and analyzed overall and each group of semaglutide adverse events.Results A total of 5 330 cases and 15 558 adverse events were collected.2 935 patients aged 18-64 old group years with 8 553 adverse events;2 395 patients aged≥65 years old group with 7 005 adverse events.2 231 male group patients with 6 195 adverse events;3 059 female group patients with 9 277 adverse events.The sex of 40 patients was unknown.Nausea(1 089 cases/7.00%),vomiting(775 cases/4.98%)and diarrhoea(545 cases/3.50%)remained the most common adverse events.The constituent ratio of pancreatitis was significantly higher in patients aged 18-64 years old group than in patients aged 65 years old group(P<0.05);the constituent ratio of diarrhoeaand cholelithiasis was significantly lower in patients aged 18-64 years old group than patients aged≥65 years old group(P<0.05).The constituent ratio of diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,diabetic retinopathy,and acute kidney injurywas significantly higher in male group patients than in female group(P<0.05).Conclusion Nausea,diarrhoea and vomiting remined the most common adverse events of semaglutide.Male should be more concerned about gastrointestinal,pancreatitis,gallbladder events,retinopathy and acute kidney injury.Elderly patients should be more alert diarrhoea and cholelithiasis.
6.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
7.Therapeutic effects of paeoniflorin on thromboangiitis obliterans model rats by regulating PI3K/AKT/NF-κB signaling pathway
Ya-Na WANG ; Xiao-Lin XU ; Wen-Hua MA ; Luo-Fang CUI ; Li LIU ; Lin-Li XU ; Yan ZHANG ; Xiu-Lei ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(6):854-858
Objective To investigate the therapeutic effect and mechanism of paeoniflorin(PAE)on thrombosis angiitis obliterans(TAO)in rats.Methods TAO rat model was established by sodium laurate injection.Rats were randomly divided into sham operation group(intraperitoneal injection of 0.9%NaCl),model group(intraperitoneal injection of 0.9%NaCl),experimental-L,-H groups(intraperitoneal injection of PAE 5,20 mg·kg-1·d-1),experimental-H+agonist group(intraperitoneal injection of 20 mg·kg-1·d-1 PAE+caudal vein injection of 10 ng·mL-1·kg 1·d-1 740 Y-P).Thrombin time(TT)was measured by magnetic bead coagulation;the levels of interleukin(IL)-1 β and endothelin 1(ET-1)were detected by enzyme-linked immunosorbent assay kit;the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated-PI3K(p-PI3 K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,p-NF-κB p65 were detected by Western blotting.Results The TT of sham operation group,model group,experimental-L,-H groups and experimental-H+agonist group were(14.88±1.32),(10.02±0.95),(12.65±1.22),(14.70±1.36)and(10.64±1.21)s;IL-1β were(154.23±13.45),(356.69±31.17),(268.62±23.58),(199.64±20.87)and(337.48±31.46)pg·mL-1;ET-1 were(6.78±0.68),(14.43±1.14),(11.23±1.07),(8.20±0.81)and(13.33±1.27)pg·mL-1;p-PI3K/PI3K were 0.36±0.04,0.76±0.07,0.59±0.05,0.44±0.04 and 0.69±0.07;p-AKT/AKT were 0.52±0.05,0.90±0.09,0.74±0.08,0.61±0.06 and 0.86±0.08;p-NF-κB p65/NF-κB p65 were 0.28±0.03,0.95±0.04,0.69±0.07,0.35±0.05 and 0.87±0.08,respectively.There were statistically significant differences between model group and sham operation group(all P<0.05);the above indexes in experimental-L group and experimental-H group were significantly different from those in medel group(all P<0.05);the above indexes in experimental-H+agonist group were significantly different from those in experimental-H group(all P<0.05).Conclusion PAE may improve disease progression in TAO rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.
8.Clinical Significance of Genetic and Molecular Changes in Primary Myeloid Sarcoma
Ya-Jun JIANG ; Chun-Fang ZHANG ; Hong-Xia WANG ; Lan ZHAO ; Fei-Fei ZHANG ; Xiu-Hua HAN
Journal of Experimental Hematology 2024;32(1):27-32
Objective:To investigate the clinical significance of genetic and molecular changes in primary myeloid sarcoma(MS).Methods:Fourteen patients with primary MS were selected in Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences,The First People's Hospital of Lianyungang from September 2010 to December 2021.AML1-ETO fusion,PML-RARα fusion and CBFβ breakage were detected by fluorescence in situ hybridization(FISH),and the mutations of NPM1,CEBPA,FLT3,RUNX1,ASXL1,KIT and TP53 genes were detected by new generation sequencing(NGS).Results:Among 14 patients,the MS occurred in bone,breast,epididymis,lung,chest wall,cervix,small intestine,ovary,lymph nodes and central nervous system.The tumor cells expressed MPO(13 cases),CD34(7 cases),CD43(8 cases),CD68(7 cases),CD99(8 cases)and CD117(6 cases).Cytogenetic abnormalities were observed in 4 cases,including 3 cases of AML1-ETO fusion and 1 case of CBF β breakage,while no PML-RAR α fusion was detected.There were no significant differences in overall survival(OS)and leukemia-free survival(LFS)between patients with and without AML1-ETO fusion/CBFβ breakage(both P>0.05).Among the 14 patients,the number of NPM1,CEBPA,FLT3-ITD,RUNX1,ASXL1,KIT and TP53 gene mutations was 5,3,5,3,2,2,1.respectively,of which 7 cases had at least one mutation in FLT3-ITD,RUNX1,ASXL1 and TP53 gene.The OS and LFS of patients with FLT3-ITD,RUNX1,ASXL1 or TP53 mutation were shorter than those without mutations(both P<0.01).Conclusion:The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques.FLT3-ITD,RUNX1,ASXL1 or TP53 mutation indicates a worse prognosis,but further clinical studies are needed to confirm it.
9.Effect of L-Type Amino Acid Transporter 1 Expression on Clinicopathological Features and Prognosis of Non-Hodgkin's Lymphoma
Zhi-Fang ZHAO ; Xiu-Jun HAO ; Yan-Min YANG ; Wei-Ge XU ; Yun-Xiao ZHANG ; Xian-Hua YUAN
Journal of Experimental Hematology 2024;32(2):434-438
Objective:To detect the expression of L-type amino acid transporter 1(LAT1)in non-Hodgkin's lymphoma(NHL)tissues,and analyze its effect on clinicopathological characteristics and prognosis of patients.Methods:A total of 92 NHL patients who were treated in our hospital from January 2017 to April 2019 were collected.The expression of LAT1 in NHL tissue was detected by immunohistochemistry and compared between patients with different pathological features(including sex,Ann Arbor stage,extranodal infiltration,Ki-67).The risk factors affecting mortality were analyzed using univariate and multivariate Cox proportional hazards regression.Receiver operating characteristic(ROC)curve was used to detect the predictive value of percentage of LAT1-positive cells in NHL tissue for patient mortality,and analyzing the effect of percentage of LAT1-positive cells on survival rate.Results:LAT1 was positively expressed in NHL tissue.The high expression rate of LAT1 in Ann Arbor stage Ⅲ and Ⅳ groups were higher than that in Ann Arbor stage Ⅰ group,that in extranodal infiltration group was higher than non-extranodal infiltration group,and that in Ki-67 positive expression group was higher than Ki-67 negative expression group(all P<0.05).The remission rate after 3 courses of treatment in high-LAT1 expression group was 70.7%,which was lower than 91.2%in low-LAT1 expression group(P<0.05).Ann Arbor stage Ⅲ and Ⅳ,extranodal invasion,Ki-67 positive expression and increased expression of LAT1(LAT1-positive cell percentage score ≥ 2)were risk factors for mortality.The cut-off value of percentage of LAT1-positive cells for predicting NHL death was 45.6%,and the area under the ROC curve was 0.905(95%CI:0.897-0.924).The 3-year survival rate of high-LAT1 level group(the percentage of LAT1-positive cells ≥ 45.6%)was 50.00%,which was lower than 78.26%of low-LAT1 level group(P<0.05).Conclusion:The expression level of LAT1 in NHL tissue increases,which affects Ann Arbor stage and extranodal infiltration of patients.LAT1 is a risk factor for death.
10.Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma
Qing-Fen LI ; Qi-Ke ZHANG ; Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Yang-Yang ZHAO ; Xiu-Juan HUANG
Journal of Experimental Hematology 2024;32(2):499-504
Objective:To analyze the prognostic nutritional index(PNI),controlling nutritional status(CONUT)and fibrinogen/albumin ratio(FAR)levels in elderly patients with multiple myeloma(MM)and their prognostic impact.Methods:The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed.The optimal cut-off values for PNI,CONUT score and FAR were obtained by receiver operating characteristic(ROC)curve,which were used for grouping patients.The correlation of above three indexes with clinical parameters such as sex,serum calcium(Ca),β2-microglobulin(β2-MG),serum creatinine(Cr)in elderly MM patients were analyzed.The survival rates of patients with different levels of each index were compared.Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed.Results:The optimal cut-off values for PNI,CONUT score and FAR were 39.775,3.5 and 0.175,respectively,according to which the patients were divided into high and low group.Statistical analysis showed that there were significant differences in albumin level among different groups(all P<0.05).In addition,there was a significant difference in hemoglobin between high-PNI group and low-PNI group(P<0.05),while in sex distribution between high-FAR and low-FAR group(P<0.05).The survival rate of elderly MM patients with increased PNI,decreased CONUT score and FAR was higher(all P<0.05).Univariate and multivariate analysis showed that β2-MG,Cr,PNI,CONUT score and FAR were independent prognostic factors for elderly MM patients.Conclusion:PNI,CONUT score and FAR are related to some clinical indicators of elderly MM patients,and have an impact on the prognosis.

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