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.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
3.Magnetic stimulation combined with moxibustion improves mild to moderate overactive bladder and sexual function in women
Dan ZHOU ; Jia-Wei WANG ; Si-Jing WANG ; Chao-Liang SHI ; Guo-Wei SHI ; Yang-Yun WANG ; Ke XU
National Journal of Andrology 2024;30(3):249-253
Objective:To investigate the clinical effect of magnetic stimulation combined with moxibustion on mild to moderate overactive bladder(OAB)and sexual function in women.Methods:We enrolled 80 female patients with mild to moderate OAB in this study and equally randomized them into a control and an experimental group,the former treated by magnetic stimulation and the latter by magnetic stimulation combined with moxibustion,both for 8 weeks.We obtained from the patients their OAB syndrome scores(OABSS),72-hour urination diary(72-h UD)scores,International Consultation on Incontinence Questionnaire-Overactive Bladder(ICIQ-OAB)scores and female sexual function indexes(FSFI),and compared them between the two groups before and after interven-tion.Results:A total of 77 patients completed the study,37 in the control and 40 in the experimental group.There were no statisti-cally significant differences in the baseline data between the two groups(P>0.05).Compared with the baseline,the experimental group showed significant improvement after treatment in the OABSS(7.54±1.12 vs 4.46±0.96),72-h urine volume([126.40±46.04]vs[216.63±38.26]ml),urination frequency(15.55±3.21 vs 8.03±1.40),ICIQ-OAB score(10.25±1.15 vs 6.32±1.07)and FSFI(20.00±12.40 vs 33.30±21.00)(all P<0.05),even more significantly than in the control group(OABSS:4.46±0.96 vs 5.59±0.90;72-h urine volume:[216.63±38.26]vs[173.41±15.55]ml;urination frequency:8.03±1.40 vs 9.90±1.49;ICIQ-OAB score:6.32±1.07 vs 7.89±0.77;FSFI:33.30±21.00 vs 30.40±10.40)(all P<0.01).Conclu-sion:Magnetic stimulation combined with moxibustion can improve the symptoms of mild to moderate overactive bladder and improve sexual function in females.
4.Selection of postoperative adjuvant therapy for patients with stage IB lung adenocarcinoma:analysis of 653 cases
Leilei SHEN ; Ying CHEN ; Tianyang YUN ; Juntang GUO ; Xi LIU ; Tao ZHANG ; Chaoyang LIANG ; Yang LIU
Journal of Southern Medical University 2024;44(5):989-997
Objective To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma.Methods We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January,2013 to December,2021.The 5-year disease-free survival(DFS)and overall survival(OS)rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors(EGFR-TKIs group,n=111),chemotherapy(CT group,n=108)and clinical observation(CO group,n=434).Results In TKIs,CT,and CO groups,the 5-year DFS rates were 92.8%,80.7%,and 81.7%,respectively,significantly higher in TKIs group than in CO group(P<0.01).The 3-year OS rates of the 3 groups were 96.8%,97.1%,and 91.7%,respectively.Subgroup analysis showed that in TKIs,CT,and CO groups,the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%,84.0%,and 81.4%,respectively,significantly higher in TKIs group than in CO group(P<0.05);the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%,71.4%,and 83.5%,respectively.Multivariate COX regression analysis showed that age(P<0.05;HR=0.631,95%CI:0.401-0.993),solid nodules(P<0.01;HR=7.620,95%CI:3.037-19.121),micropapillary or solid component(P<0.05;HR=1.776,95%CI:1.010-3.122),lymphovascular invasion(P<0.05;HR=2.981,95%CI:1.198-7.419),and adjuvant therapy(P<0.01)were independent predictors of DFS.The most common adverse effects included rashes,paronychia,and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy,and TKIs were associated with a higher incidence of grade 3 or above adverse effects(44.4%vs 9.0%).Conclusion Adjuvant therapy with TKIs helps improve DFS in patients with stage IB(T3-4cmN0M0)lung adenocarcinoma but not in patients with T2ViscPlN0M0.Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.
5.YANG Wen-Hui's Experience in Treating Lumbago Disease with YANG's Baliao-Acupoints Moxibustion
Dang-Han XU ; Zhao-Xi LIU ; Guo-Ji LIN ; Liang ZHENG ; Yun-Xuan HUANG ; Chun-Lin WEN ; Fang FANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(11):2973-2979
The experience of professor YANG Wen-Hui in treating lumbago disease with YANG's Baliao-acupoints moxibustion is introduced in this paper.YANG Wen-Hui believes that the basic pathogenesis of lumbago disease is'cold causes lower back pain',and based on the philosophical idea of'harmony in Shushu(the ways to cultivate health)',he proposes'YANG's Baliao-acupoints moxibustion'for the treatment of lumbago disease.According to the patient's condition,professor YANG used the acupoints of Shangliao(BL31),Ciliao(BL32),Zhongliao(BL33),and selected the moxa cone like jujube core,soybean or wheat grain,and applied moxibustion with the technique of'San Yang Kai Tai'or'Ruo feng Chui Yun',the number of moxibustion is proportional to the age of the patient.YANG's Baliao-acupoints moxibustion in treating lumbago disease exerts highly and remarkable clinical efficacy,and it was widely acclaimed by the patients.
6.Selection of postoperative adjuvant therapy for patients with stage IB lung adenocarcinoma:analysis of 653 cases
Leilei SHEN ; Ying CHEN ; Tianyang YUN ; Juntang GUO ; Xi LIU ; Tao ZHANG ; Chaoyang LIANG ; Yang LIU
Journal of Southern Medical University 2024;44(5):989-997
Objective To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma.Methods We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January,2013 to December,2021.The 5-year disease-free survival(DFS)and overall survival(OS)rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors(EGFR-TKIs group,n=111),chemotherapy(CT group,n=108)and clinical observation(CO group,n=434).Results In TKIs,CT,and CO groups,the 5-year DFS rates were 92.8%,80.7%,and 81.7%,respectively,significantly higher in TKIs group than in CO group(P<0.01).The 3-year OS rates of the 3 groups were 96.8%,97.1%,and 91.7%,respectively.Subgroup analysis showed that in TKIs,CT,and CO groups,the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%,84.0%,and 81.4%,respectively,significantly higher in TKIs group than in CO group(P<0.05);the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%,71.4%,and 83.5%,respectively.Multivariate COX regression analysis showed that age(P<0.05;HR=0.631,95%CI:0.401-0.993),solid nodules(P<0.01;HR=7.620,95%CI:3.037-19.121),micropapillary or solid component(P<0.05;HR=1.776,95%CI:1.010-3.122),lymphovascular invasion(P<0.05;HR=2.981,95%CI:1.198-7.419),and adjuvant therapy(P<0.01)were independent predictors of DFS.The most common adverse effects included rashes,paronychia,and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy,and TKIs were associated with a higher incidence of grade 3 or above adverse effects(44.4%vs 9.0%).Conclusion Adjuvant therapy with TKIs helps improve DFS in patients with stage IB(T3-4cmN0M0)lung adenocarcinoma but not in patients with T2ViscPlN0M0.Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.
7.Curcumol Mediates the Programmed Cell Death in Acute Myeloid Leukemia through PI3K/AKT Signaling Pathway
Zuo-Tao LI ; Xiao-Yun CHEN ; Hai-Liang LI ; Gui-Xiang LENG ; Yan-Quan LIU ; Ling GUO ; Yi-Li WANG
Journal of Experimental Hematology 2024;32(6):1682-1688
Objective:To investigate the effects of Curcumol on the malignant biological characteristics of acute myeloid leukemia (AML)cells and its molecular mechanism,and to provide theoretical and experimental evidence for the anti-leukemia treatment of traditional Chinese medicine.Methods:After the AML cell lines HL-60 and KG-1 cells were treated different concentrations of with Curcumol.The proliferation activity of cells was detected by CCK-8 method,and the expression changes of apoptotic proteins and PI3 K/AKT signaling pathway proteins were detected by Western blot. Real-time quantitative fluorescence polymerase chain reaction (RT-qPCR ) was used to detect the expression of Caspase family mRNA.Results:Curcumol could inhibit the proliferation and induce apoptosis of HL-60 and KG-1 cells,promote apoptosis by up-regulating the expression of Bax and down-regulating the expression of Bcl-2 protein (P<0.05).When Curcumol interferes with HL-60 and KG-1 cells,it can also induce programmed cell death of AML by inhibiting PI3 K/AKT signaling pathway.In addition,after the intervention of Curcumol,the expression of Caspase 3,Caspase 6,Caspase 8 and Caspase 9 were up-regulated in HL-60 cells (P<0.05 ),the expression of Caspase 3,Caspase 8 and Caspase 9 were significantly up-regulated in KG-1 cells (P<0.01),while the expression of Caspase 6 was weakly affected (P<0.05 ),but low concentration of Curcumol (<60 μg/ml)had no effect on the expression of Caspase 6 in KG-1 cells (P>0.05).Conclusion:Curcumol may mediate the programmed death of AML cells by inhibiting the PI3K/AKT signaling pathway,affecting the expression of Bcl-2 family proteins,and promoting the activation of core members of Caspase family,so as to play an anti-leukemia role.
8.Expert consensus on clinical application of Lixuwang~® Xuesaitong Soft Capsules.
Min JIA ; Xiao LIANG ; Guo-Jing FU ; Xiang-Lan JIN ; Yan LU ; Xing LIAO ; Yun-Ling ZHANG
China Journal of Chinese Materia Medica 2023;48(20):5668-5674
Lixuwang~® Xuesaitong Soft Capsules(referred to as "Xuesaitong Soft Capsules") have the effects of promoting blood circulation, resolving blood stasis, and dredging meridians and collaterals. They are widely used in the prevention and treatment of cardiovascular and cerebrovascular diseases in clinical practice. Through years of clinical observation, they have shown significant efficacy in ischemic stroke, coronary heart disease, and other diseases, and have been recommended by multiple guidelines, consensus statements, and monographs. Based on the summary of clinical application experience by doctors and existing evidence-based research, following the Technical Specifications for Consensus Development of Chinese Patent Medicine by Clinical Experts issued by Standardization Office of the Chinese Association of Traditional Chinese Medicine, a nominal group method was used to reach 19 recommended opinions/consensus suggestions. This document proposes the timing of medication, syndrome differentiation for medication, therapeutic effects, dosage and administration, treatment duration, economic considerations, and safety considerations in the use of Xuesaitong Soft Capsules for the treatment of ischemic stroke and angina pectoris in coronary heart disease. It is intended for doctors in internal medicine, encephalopathy(neurology), cardiovascular medicine, geriatrics, emergency medicine, general practice, and traditional Chinese medicine departments of various medical institutions, as well as pharmacists in hospitals and pharmacies, as a medication reference when using Xuesaitong Soft Capsules. It is hoped that the widespread application of this consensus can improve the clinical efficacy of Xuesaitong Soft Capsules in the treatment of ischemic stroke and coronary heart disease, promote rational drug use, and reduce medication risks. This consensus has been reviewed and published by the China Association of Traditional Chinese Medicine, with the identification number GS/CACM 323-2023.
Humans
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Consensus
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Drugs, Chinese Herbal/therapeutic use*
;
Medicine, Chinese Traditional
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Coronary Disease/drug therapy*
;
Ischemic Stroke/drug therapy*
;
Capsules
9.Analysis of the causes of soft tissue complications after volar locking plate for the treatment of dorsal displaced distal radius fractures.
Jin-Gu TAI ; Zhi-Yong DING ; Liang SUN ; Yun-Ping CAO ; Guo-Bao YE ; Peng HAO ; Wei LI
China Journal of Orthopaedics and Traumatology 2023;36(9):839-845
OBJECTIVE:
To investigate the causes of soft tissue complications in patients with dorsal displacement distal radius fractures (DRF) after volar locking plate surgery.
METHODS:
From July 2016 to May 2021, 112 patients with dorsal displacement DRF were treated with volar locking plate surgery, including 45 males and 67 females. The average age was (46.24±10.08) years old, ranging from 18 to 85 years old. According to whether there were soft tissue complications after operation, they were divided into complication group (40 cases) and non complication group (72 cases). Compared with preoperation, the radial metacarpal inclination and ulnar deflection angle, wrist flexion activity and dorsal extension activity, and grip strength of patients after operation were significantly improved (P<0.05). Compared with the non complication group, the proportion of patients in the complication group whose age was>60 years, body mass index (BMI) more than 30 kg·m-2, smoking, diabetes, fracture type C, open fracture and operation time more than 90 min was higher (P<0.05). The age, BMI, smoking, diabetes, fracture AO classification, fracture type and operation time were analyzed by multifactor Logistic regression to determine the independent risk factors affecting the occurrence of postoperative soft tissue complications of patients, establish a nomogram prediction model, and evaluate the model.
RESULTS:
At the latest follow-up, the excellent and good rate of wrist joint function recovery was 83.93% (94/112), and the excellent and good rate of fracture reduction was 84.82% (95/112). Multivariate Logistic regression analysis showed that age more than 60 years old, diabetes, fracture type C, open fracture and operation time more than 90 min were independent risk factors for postoperative soft tissue complications (P<0.05). The receiver operating characteristic (ROC), calibration curve and clinical decision curve of the nomogram prediction model showed discrimination, accuracy and validity were good.
CONCLUSION
Age more than 60 years, diabetes mellitus, fracture type C, open fracture, and operation time more than 90 min are all independent risk factors for soft tissue complications after DRF volar plate fixation. In clinical treatment, perioperative soft tissue management should be done in such patients to prevent complications.
Female
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Male
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Humans
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Adult
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Middle Aged
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Adolescent
;
Young Adult
;
Aged
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Aged, 80 and over
;
Wrist Fractures
;
Fractures, Open
;
Risk Factors
;
Wrist Joint/surgery*
;
Metacarpal Bones
10. Expression, purification and functional verification of recombinant human α-galactosidase A in suspension CHO-S
Mu-Lan DENG ; Hong-Yu ZHOU ; Ke-Xin ZHENG ; Zhao-Yang LI ; Wan-Yi GUO ; Yan-Ping WANG ; Zhi-Cheng LIANG ; Fang-Hong LI ; Yun-Ping MU ; Zi-Jian ZHAO
Chinese Pharmacological Bulletin 2023;39(4):774-781
Aim To express and purify rhα-Gal A with a 6 X His tag via using a serum-free expression system in high-density suspension culture of Chinese hamster ovary cells ( CHO-S) , and to verify the scavenging effect of rhα-Gal A on globular trisaccharide ceramide (Gb3 or GL3) . Methods The construction of recombinant protein expression vector, pcDNA4-GLA, was achieved by fusing the human α-galactosidase cDNA, gla, with 6 X His tag and artificial DNA synthesis. The expression plasmid was transfected into the suspended CHO-S to express rhα-Gal A and then purified. Following this procedure, we determined rhα-Gal A's expression, the enzymatic activity, and the glycosylation of the recombinant enzyme. Co-incubation with cultured cells was performed to examine whether rhα-Gal A could be taken up into the cells and effectively remove Gb3 substrates. Results rhα-Gal A was successfully expressed and purified after transiently transfecting pcDNA4-GLA into the suspended CHO-S, and the yield was up to (100 ±20. 6) mg • L

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