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.Analysis of Knowledge Map of Acupoint Catgut Embedd Therapy for Pain Based on Citespace
Hong-Fen YI ; Xin-Yu CHEN ; Han PENG ; Qian LI ; Tao-Hong LUO ; Qing-Long XUE ; Hao-Lin ZHANG ; Jian ZHUANG ; Mai-Lan LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):154-160
Objective To comprehensively excavate and analyze the research status,research hotspots and future trends of the literature related to the field of acupoint catgut embedding therapy for pain treatment in the CNKI database.Methods We searched the CNKI database from its establishment to June 2022,and scientifically analyzed the authors,keywords,and institutions of the included literature of acupoint catgut embedding therapy for pain treatment through specific algorithms of Citespace to generate a visual knowledge map.Results A total of 319 documents were included for statistical analysis,the number of publications in the field of acupoint catgut embedding therapy for the treatment of pain was generally on the rise,the number of publications by various authors was on the low side,and there was a lack of co-operation between the research teams,with the main institutions being the Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Affiliated Hospital of Youjiang Medical Universities of Nationalities and the Guangzhou University of Chinese Medicine,forming a 10-keyword clustering,and the hotspots of diseases under study were mainly mixed haemorrhoids,postoperative pain,low back and leg pain and dysmenorrhoea,etc..The main interventions were pure acupoint catgut embedding therapy and the combination of acupoint catgut embedding therapy and other acupuncture therapies,and the main research method was clinical research.Conclusion Acupoint catgut embedding therapy for the treatment of pain has a good development prospect,the future needs to deepen the clinical research,strengthen the mechanism research,pay attention to the joint use of acupoint catgut embedding therapy and other traditional Chinese medicine methods,and pay attention to the research of different thread materials.
3.Efficacy and safety of decitabine combined with unrelated umbilical cord blood transplantation in the elderly patients with acute myeloid leukemia after achieving remission
Can CHEN ; Yong-Fen HUANG ; Ling-Ling WANG ; Ya-Nan MA ; Yue-Xin CHENG ; Hao XU ; Shan-Dong TAO ; Yu-Qing MIAO
Chinese Journal of Clinical Medicine 2023;30(6):981-987
Objective To compare the safety and efficacy of decitabine combined with unrelated umbilical cord blood transplantation and traditional regimen in the elderly patients with acute myeloid leukemia(AML)after achieving complete remission with induction therapy.Methods Fifty-two elderly AML patients who obtained complete remission(CR)after 1-2 cycles of induction therapy in the Department of Hematology of Yancheng First People's Hospital and the Huai'an First Hospital Affiliated to Nanjing Medical University from January 2019 to January 2022 were enrolled,and were divided into the observation group(n=24)and the control group(n=28).The observation group received decitabine combined with unrelated umbilical cord blood transplantation,and the control group received traditional consolidation therapy,including azacitidine+vinblastine,idarubicin+cytarabine(IA),or aclarubicin+cytarabine+granulocyte colony-stimulating factor,and so on.The hematopoietic recovery time,adverse reactions,relapse-free survival(RFS),and overall survival(OS)were compared between the two groups.Results The median recovery time of neutrophils was 12.54 d in the observation group and wes 18.64 d in the control group(P<0.001);the median recovery time of platelets was 12.67 d in the observation group and was 19.71 d in the control group(P<0.001).There was no difference in incidences of grade Ⅲ-Ⅳ myelosuppression and non-hematological toxicity between the two groups.There were statistical differences in the median RFS(33 months vs 11 months)and OS(36 months vs 24 months)between the observation group and the control group(P<0.05).Conclusions Compared with the traditional consolidation regimen,decitabine combined with unrelated umbilical cord blood transplantation for consolidation of AML after achieving remission is more effective in elderly patients,could prolong survival,and has similar safety.
4.Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.
Yuan Yue ZHU ; Rui Zhi ZHENG ; Gui Xia WANG ; Li CHEN ; Li Xin SHI ; Qing SU ; Min XU ; Yu XU ; Yu Hong CHEN ; Xue Feng YU ; Li YAN ; Tian Ge WANG ; Zhi Yun ZHAO ; Gui Jun QIN ; Qin WAN ; Gang CHEN ; Zheng Nan GAO ; Fei Xia SHEN ; Zuo Jie LUO ; Ying Fen QIN ; Ya Nan HUO ; Qiang LI ; Zhen YE ; Yin Fei ZHANG ; Chao LIU ; You Min WANG ; Sheng Li WU ; Tao YANG ; Hua Cong DENG ; Jia Jun ZHAO ; Lu Lu CHEN ; Yi Ming MU ; Xu Lei TANG ; Ru Ying HU ; Wei Qing WANG ; Guang NING ; Mian LI ; Jie Li LU ; Yu Fang BI
Biomedical and Environmental Sciences 2021;34(1):9-18
Objective:
The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.
Methods:
The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.
Results:
A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).
Conclusion
An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged
;
Asian Continental Ancestry Group
;
Blood Glucose/analysis*
;
China/epidemiology*
;
Cohort Studies
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Diabetes Mellitus/blood*
;
Female
;
Glucose Tolerance Test
;
Glycated Hemoglobin A/analysis*
;
Glycemic Index
;
Humans
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Male
;
Middle Aged
;
Uric Acid/blood*
5.Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing
Hai-Yun WANG ; Ling DENG ; Ying-Qing LI ; Xiao ZHANG ; Ya-Kang LONG ; Xu ZHANG ; Yan-Fen FENG ; Yuan HE ; Tao TANG ; Xin-Hua YANG ; Fang WANG
Cancer Research and Treatment 2021;53(4):973-982
Purpose:
Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice.
Materials and Methods:
TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate.
Results:
The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs.
Conclusion
Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.
6.A clinical epidemiological investigation of neonatal acute respiratory distress syndrome in southwest Hubei, China.
Yong-Fang ZHANG ; Xin-Qiao YU ; Jian-Hua LIAO ; Feng YANG ; Cong-Rong TAN ; Su-Ying WU ; Shi-Qing DENG ; Jun-Yuan FENG ; Jia-Yan HUANG ; Zuo-Fen YUAN ; Kai-Dian LIU ; Zhen-Ju HUANG ; Li-Fang ZHANG ; Zheng-Guo CHEN ; Hong XIA ; Lin-Lin LUO ; Yan HU ; Hua-Sheng WU ; Hong-Ling XIE ; Bao-Min FEI ; Qing-Wei PANG ; Song-Hua ZHANG ; Bi-Xia CHENG ; Lang JIANG ; Chang-Tao SHEN ; Qiong YI ; Xiao-Guang ZHOU
Chinese Journal of Contemporary Pediatrics 2020;22(9):942-947
OBJECTIVE:
To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China.
METHODS:
According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017.
RESULTS:
A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66).
CONCLUSIONS
Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.
China
;
Female
;
Humans
;
Infant, Newborn
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Meconium Aspiration Syndrome
;
Pregnancy
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Respiratory Distress Syndrome, Newborn
;
Retrospective Studies
7.Establishment of clinical features and prognostic scoring model in early-stage hepatitis B-related acute-on-chronic liver failure
Tianzhou WU ; Xi LIANG ; Jiaqi LI ; Tan LI ; Lingling YANG ; Jiang LI ; Jiaojiao XIN ; Jing JIANG ; Dongyan SHI ; Keke REN ; Shaorui HAO ; Linfeng JIN ; Ping YE ; Jianrong HUANG ; Xiaowei XU ; Zhiliang GAO ; Zhongping DUAN ; Tao HAN ; Yuming WANG ; Baoju WANG ; Jianhe GAN ; Tingting FEN ; Chen PAN ; Yongping CHEN ; Yan HUANG ; Qing XIE ; Shumei LIN ; Xin CHEN ; Shaojie XIN ; Lanjuan LI ; Jun LI
Chinese Journal of Hepatology 2020;28(4):310-318
Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.
8.Research progress of Pickering emulsion drug delivery systems
Ji-fen ZHANG ; Yan-hua WANG ; Qing-qing LI ; Fan WANG ; Tao YI
Acta Pharmaceutica Sinica 2019;54(12):2232-2239
Pickering emulsion is a new type of emulsion which is stabilized by the adsorption of solid particles on the interface of emulsion droplets. In recent years, its applications in pharmacy have attracted more and more attention because of its higher resistance to coalescence and better safety than traditional surfactant emulsions. The Pickering emulsion was first used for topical administration to reduce skin irritation of surfactants and promote transdermal absorption of drugs. Recently, new oral and injectable Pickering emulsions have also been reported, which can promote oral absorption of insoluble drugs, improve stability of drugs, control drug release, targeted-delivery drugs, and serve as the carrier for novel immunological adjuvants. All these studies show Pickering emulsion a promising drug delivery system. However, its development in pharmacy is still in its infancy. There are many factors influencing the preparation of Pickering emulsions. But there is no systematic analysis of these factors up to now. In this review, we gave an overview of Pickering emulsions from their application in pharmaceutical field, preparation and evaluation, focusing on the effects of solid particles, oil phase, preparation technology and interaction of various factors on the fabrication of Pickering emulsions. The challenges and future directions of this exciting and rapidly expanding research area were further commented on, in order to provide reference for the in-depth study of Pickering emulsion drug delivery systems.
9.Intestinal absorption of puerarin nanocrystalline self-stabilizing pickering emulsion in rats.
Shuai WANG ; Qing-Qing LI ; Fan WANG ; Tao YI ; Ji-Fen ZHANG
China Journal of Chinese Materia Medica 2018;43(10):2162-2167
To study the intestinal absorption characteristics of drug's nanocrystalline self-stabilizing Pickering emulsion (NSSPE) in situ in rats. Rat single-pass intestinal perfusion model was established, and high performance liquid chromatography (HPLC) was used to detect the concentration of puerarin in rat intestinal perfusion solution, assay the absorption rate constant (Ka) and the intestinal apparent permeability coefficient (Papp) of NSSPE in duodenum, jejunum, ileum, and colon, which were compared with those of raw material, nanocrystal and normal emulsion, respectively. For NSSPE, the Ka and Papp values were in the following order: duodenum>jejunum>ileum (<0.05)>colon (<0.01). However, there was no obvious difference between jejunum and ileum. As compared with raw material, nanocrystal and normal emulsion, the Ka and Papp values of NSSPE in duodenum were significantly higher than those of other three preparations (<0.05); and the Ka and Papp values of NSSPE in jejunum and colon were significantly higher than those of raw material, nanocrystal and normal emulsion (<0.01); and the Ka and Papp of NSSPE in ileum were also higher than those of raw material and normal emulsion (<0.05), but had no obvious difference with nanocrystal. The results showed that NSSPE could significantly improve the absorption of puerarin in the intestine of rats.
10.Application of sedation-agitation scale in children's conscious sedation before broncoscopy examination
Lin ZHONG ; Li-Na CHEN ; Ting CHEN ; Qing-Fen TAO ; Song-Hui ZHAI ; Li QIU
China Journal of Endoscopy 2018;24(2):1-5
Objective To explore the application value of sedation-agitation scale (SAS) in broncoscopy in children by observing sedative drug dosage, adverse reactions and operator's satisfaction. Methods Children were divided into two groups, control group and SAS group, before broncoscopy. Midazolam was given a dose 0.10 ~ 0.30 mg/kg according to doctor's experience, without any assessment, while the SAS group were given an initial doses of Midazolam 0.10 mg/kg and then continued giving Midazolam until the SAS score reached 3 points to 4 points, but the maxium does less than 10 mg. The maxium dosage of Midazolam in both groups was less than 10 mg. Then compare the dosage and adverse reactions of Midazolam and operator's satisfaction between the two groups. Results 606 children were enrolled in the study, 364 were boys and 242 were girls. The age ranged from 1 month to 17 years, while the mean age was (3.97 ± 3.94) years. The body weights were from 2.4 kg to 56.0 kg, and the mean weight was (16.18 ± 10.65) kg. 301 children were included into control group and 305 children were included into SAS group. The gender composition, age range, department source and composition of the diseases of the two groups were compared, and the differences were not statistically significant. Compared with the control group, there was no severe adverse reaction such as respiratory depression or excessive sedation in the SAS group, and the average amount of Midazolam was lower than the dosage in control group [(0.21 ± 0.06) vs (0.26 ± 0.05) mg/kg];the intraoperative agitation, delirium, other adverse drug reactions and the number of involved in the operation, and operation time were reduced, while the differences were statistically significant. The operator's satisfaction is higher, but the difference was not statistically significant. Conclusions SAS can be used in assessment of conscious sedation level in children's bronchoscopy, and SAS can guide the individual use of Midazolam, reduce its dosage and adverse reactions,also can improve the operator's satisfaction during the operation. SAS is worthy of application in children's conscious sedation in bronchoscopy.

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