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.Urinary iodine characteristics of children aged 8 to 10 in Jiangxi Province in 2022
Jun SHANGGUAN ; Binghua ZHOU ; Qiang HU ; Meiqin HUANG ; Guai TANG ; Yanfeng GONG ; Zifen LI ; Wenfang PENG
Chinese Journal of Endemiology 2024;43(10):823-825
Objective:To study the urinary iodine levels of children in Jiangxi Province and provide a basis for prevention and treatment of iodine deficiency disorders and scientific iodine supplementation.Methods:From March to July in 2022, a systematic sampling method was used in 99 counties (cities, districts, abbreviated as counties) in Jiangxi Province. One township (street) was selected from each county in five directions: east, west, south, north and middle. One primary school was selected from each township (street), and 40 non boarding children aged 8 - 10 (half male and half female) were selected from each primary school. One random urine sample was collected to test urinary iodine, and the distribution of urinary iodine in different regions, genders, and ages were compared.Results:A total of 19 842 urine samples were collected from children, with a median urinary iodine level of 181.90 μg/L. The median urinary iodine levels of children in different cities ( H = 1 014.05, P < 0.001), genders ( Z = 6.44, P < 0.001) and ages groups ( H = 29.82, P < 0.001) were compared, and the differences were statistically significant. Conclusion:The urinary iodine level of children in Jiangxi Province is at an appropriate level, but the distribution of urinary iodine is uneven among different regions, genders, and ages, indicating that scientific and precise iodine supplementation is necessary for the prevention and treatment of iodine deficiency disorders.
3.Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome.
Ming Sheng MA ; Zhi YANG ; Cai Hui ZHANG ; Yao Yao SHANGGUAN ; Yong Zhen LI ; Mei Fang ZHU ; Cui BAI ; Yu ZHOU ; Qiu Ye ZHANG ; Hai Guo YU ; Xiao Chuan WU ; Wen Jie ZHENG ; Jun YANG ; Hong Mei SONG
Chinese Journal of Pediatrics 2023;61(12):1098-1102
Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male
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Child
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Female
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Humans
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Child, Preschool
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Receptors, Tumor Necrosis Factor, Type I/genetics*
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Retrospective Studies
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Hereditary Autoinflammatory Diseases/drug therapy*
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Glucocorticoids/therapeutic use*
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Biological Factors/therapeutic use*
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Immunosuppressive Agents/therapeutic use*
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Autoantibodies
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Familial Mediterranean Fever/diagnosis*
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Mutation
4.Learning curve analysis and influencing factors of operation time of laparoscopic sleeve gastrectomy
Zhixin SHANGGUAN ; Qing ZHONG ; Yiming JIANG ; Chaohui ZHENG ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jun LU ; Jianxian LIN ; Changming HUANG
Chinese Journal of Digestive Surgery 2023;22(8):996-1002
Objective:To investigate the influencing factors of operation time for laparos-copic sleeve gastrectomy (LSG) and analyze the learning curve of LSG in sarcopenic obesity (SO) and non-sarcopenic obesity (NSO).Methods:The retrospective cohort study was conducted. The clinical data of 240 obesity patients who underwent LSG in the Fujian Medical University Union Hospital from January 2018 to June 2022 were collected. There were 52 males and 188 females, aged (30±8)years. Patients underwent L3 vertebral body horizontal axial computer tomography (CT) scanning before and after receiving LSG to accurately segment muscles and fats. Observation indicators: (1) treatment and follow-up; (2) influencing factors of operation time for LSG; (3) cumulative sum (CUSUM) of learning curve; (4) comparison of clinical data between patients in the initial and profi-cient stages. Measurement data with normal distribution were represent as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(IQR), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate and multivariate analyses were conducted using the Logistic regression model. The CUSUM of learning curve was calculated and the fitting process was conducted on scatter plot of learning curves. Results:(1) Treatment and follow-up. Of the 240 patients, there were 97 cases of SO and 143 cases of NSO. All 240 patients underwent LSG successfully, without conversion to open surgery. The operation time of 240 patients was (108±23)minutes. None of patient died during the perioperative period and all patients underwent follow-up during the postoperative 6 months. (2) Influencing factors of operation time for LSG. Results of multivariate analysis showed that SO was an independent factor influencing operation time for LSG ( odds ratio=2.207, 95% confidence interval as 1.207-4.038, P<0.05). (3) CUSUM of learning curve. Results of CUSUM of operation time in patients of SO and NSO showed that the best fit equation of patients of SO was y=-4E-08x 6+1E-05x 5-0.001 1x 4+0.063 1x 3-1.89x 2+28.126x-48.671 (x means the number of surgical cases), with goodness-of-fit R 2 as 0.833, and the best fit equation of patients of NSO was y=3E-09x 6-1E-06x 5+0.000 2x 4-0.010 9x 3+0.063 8x 2+12.053x-65.025 (x means the number of surgical cases), with goodness-of-fit R 2 as 0.716. Based on the trend of CUSUM of learning curve of operation time, the peak value of number of surgical cases in patients of SO and NSO was 81 and 36, respec-tively, which was used to divide the learning curve as two stages of the initial stage and the proficient stage. (4) Comparison of clinical data between patients in the initial and proficient stages. ① Of the 97 patients of SO, there were 81 cases and 16 cases in the initial stage and the proficient stage of LSG, with the operation time, postoperative duration of hospital stay as (119±23)minutes, (5.9±2.3)days and (106±21)minutes, (4.7±0.5)days, showing significant differences between them ( t=2.074, 2.147, P<0.05). ②Of the 143 patients of NSO, there were 36 cases and 107 cases in the initial stage and the proficient stage of LSG, with gender (female), height, preoperative body mass, defatted body mass, operation time, postoperative duration of hospital stay, body mass at postoperative 6 month, body mass index (BMI) at postoperative 6 month, percentage of excess weight loss (EWL%) at postoperative 6 month, cases with EWL% >100% at postoperative 6 month, excess BMI at post-operative 6 month as 20, (170±10)cm, (110±25)kg, (57±12)kg, (108±22)minutes, (6.1±1.6)days, (80±16)kg, (27.63±4.22)kg/m2, 83%±35%, 9, 1.99(6.03)kg/m2 and 87, (164±8)cm, (99±20)kg, (52±12)kg, (100±19)minutes, (4.7±1.1)days, (71±16)kg, (25.89±4.48)kg/m2, 103%±42%, 48, 0.31(5.82)kg/m2, showing significant differences between them ( χ2=9.484, t=3.266, 2.424, 2.141, 2.137, 5.821, 2.740, 1.993, -2.524, χ2=4.432, Z=-2.300, P<0.05). Conclusions:SO is an independent factor influencing operation time for LSG. It is suggested that the surgeons need to finish 81 cases and 36 cases master LSG in patients of SO and NSO.
5.Surveillance results of iodine deficiency disorders in key populations in Ganzhou City, Jiangxi Province from 2018 to 2022
Yuekang YAN ; Hongmin CAO ; Jun SHANGGUAN ; Yaoqin ZHU ; Zijuan YANG ; Rongrong YANG ; Gang DU ; Qi HUANG
Chinese Journal of Endemiology 2023;42(11):908-912
Objective:To investigate the status of iodine deficiency disorders in children and pregnant women in Ganzhou City, Jiangxi Province, and to provide a basis for scientific iodine supplementation and adjustment of prevention and control strategies.Methods:According to the requirements of the National Iodine Deficiency Disorders Surveillance Program (2016 Edition), iodine deficiency disorders surveillance was carried out in 18 counties (cities, districts) under the jurisdiction of Ganzhou City from 2018 to 2022. Edible salt and urine samples taken from children aged 8 to 10 and pregnant women were collected to detect salt and urine iodine levels. At the same time, B-ultrasound method was adopted to measure children's thyroid volume, and the goiter rate was calculated.Results:From 2018 to 2022, a total of 27 075 edible salt samples were collected from key populations (children aged 8 - 10 and pregnant women), with a median salt iodine of 25.00 mg/kg and a qualified iodized salt consumption rate of 96.24% (26 057/27 075). The difference in the qualified iodized salt consumption rate among key populations in different years was statistically significant (χ 2 = 29.09, P < 0.001). A total of 18 061 urine samples were collected from children, with a median urine iodine of 192.10 μg/L, there was a statistically significant difference in the urine iodine level of children between different years ( H = 82.59, P < 0.001). A total of 9 014 urine samples were collected from pregnant women, with a median urine iodine of 177.20 μg/L, there was a statistically significant difference in urine iodine level of pregnant women between different years ( H = 78.78, P < 0.001). A total of 8 621 children's thyroid glands were examined, including 34 cases of goiter, with a goiter rate of 0.39%, and the goiter rate showed a decreasing trend year by year (χ 2trend = 11.09, P < 0.001). Conclusions:From 2018 to 2022, the iodine nutrition of children and pregnant women in Ganzhou City is at an appropriate level, the consumption rate of qualified iodized salt (> 90%) and the children's goiter rate (< 5%) met the national iodine deficiency disorders elimination standards. Ganzhou City continues to maintain the status of eliminating iodine deficiency disorders.
6.Analysis of quality control assessment results of urine fluoride laboratories in Jiangxi Province in 2019 - 2021
Wenfang PENG ; Hong ZHOU ; Yingchun SONG ; Jun SHANGGUAN
Chinese Journal of Endemiology 2023;42(12):1017-1020
Objective:To analyze the quality control test results of urine fluoride laboratories in Jiangxi Province, and support reliable data for the monitoring and prevention of fluorosis.Methods:From 2019 to 2021, the Jiangxi provincial urine fluoride laboratories used the "Determination of Fluoride in Urine-Ion Selective Electrode Method" (WS/T 89-2015) to detect quality control samples. Origin 9 software was used to analyze the data, and Youden plots and deviation bar plots were produced. The results were evaluated based on the Z-score (qualified: │Z│ ≤2, basically qualified: 2 < │Z│ < 3, unqualified: │Z│ ≥3).Results:The qualified rate of quality control assessment results of urine fluoride laboratories in Jiangxi Province was 95.00% (38/40) . Most of urine fluoride laboratories had scores of │Z│ < 2, and two laboratories had scores │Z│≥3 in 2019 and 2020.Conclusion:The quality control assessment results of urine fluoride laboratories in Jiangxi Province are relatively satisfactory, but some laboratories still need to further improve their detection capabilities.
7. Effects of alfentanil on tracheal intubation during tonsillectomy in children: A randomized double-blind study
Jiajia LI ; Mengmeng CHEN ; Ruixian WANG ; Mengmeng HUANG ; Jun LI ; Wangning SHANGGUAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(2):184-189
AIM: To compare the effects of different doses of alfentanil on tracheal intubation conditions, hemodynamic parameters and recovery quality in children undergoing tonsillectomy. METHODS: Ninety children undergoing tonsillectomy were randomly divided into 3 groups, and received alfentanil 20 μg/kg (A20 group), 40 μg/kg (A40 group) and 60 μg/kg (A60 group) for anesthesiainduction respectively, 30 cases in each group. The remaining anesthesia induction and maintenance protocols were the same. The Helbo-Hansen scores of the three groups were evaluated, and the MAP and HR before anesthesia induction (T0), before tracheal intubation (T1), immediately after tracheal intubation (T2), and 1 min after intubation (T3) as well as the recovery time of spontaneous breathing, eye opening time, extubated time, agitation score in PACU, and adverse drug reactions were recorded. RESULTS: Compared with A20 group, the total values of Helbo-Hansen score and cough scores in group A40 and A60 were lower (P<0.05). Compared with T0, the MAP at T1-T3 were decreased in group A40 and A60, and HR increased at T2 and T3 in group A20 while HR slowed down at T1 in group A40, and at T1-T3 in group A60 (P<0.05). Compared with A20 group, children in group A40 had lower MAP and slower HR at T1-T3, while those in group A60 had lower MAP and slower HR at T1-T3 (P<0.05). The recovery time of spontaneous breathe and extubated time were prolonged in group A60 (P<0.05). CONCLUSION: During the anesthesia induction period of tonsillectomy in children, both afentanil 40 μg/kg or 60 μg/kg combined with propofol 3 mg/kg and rocuronium 0.3 mg/kg can provide satisfactory intubation condition, while the vital signs are more stable during anesthesia induction in afentanil 40 μg/kg group and rapid extubation after operation can be achieved.
8.The promotion of bone formation at the tendon-bone interface after ACL reconstruction with De-BMSCs transplantation and its mechanism
Kai TIE ; Jinghang CAI ; Jun QIN ; Hao XIAO ; Yangfan SHANGGUAN ; Liaobin CHEN
Chinese Journal of Orthopaedics 2022;42(8):519-529
Objective:This study aimed to investigate the effect of differentiation osteogenic bone marrow mesenchymal stem cells (De-BMSCs) transplantation on the promotion of bone formation at the tendon-bone interface after anterior cruciate ligament reconstruction (ACLR), and further explored the molecular mechanism of the enhanced osteogenic effect of De-BMSCs.Methods:BMSCs from femur and tibia of New Zealand White rabbit were subjected to osteogenic induction and then cultured in no osteogenic factor medium; the obtained cell population was termed De-BMSCs. De-BMSCs were induced into osteo-, chondro-and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. ACLR model with a semitendinosus tendon were performed in 48 adult rabbits, three groups were established: control group with alginate gel injectionat the tendon-bone interface, BMSCs group with the injection of alginate gel containing BMSCs, De-BMSCs group with the injection of alginate gel containing De-BMSCs. At 4 and 12 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing by histologic staining, micro-CT examination, and biomechanical test. During osteogenic differentiation of De-BMSCs, si-RNA of nuclear factor of activated T cells 2 (NFATc2) si-RNA of nuclear factor of activated T cells 1 (NFATc1) were used to verify the molecular mechanism of enhanced osteogenic effect of De-BMSCs.Results:De-BMSCs exhibited some properties similar to BMSCs including multiple differentiation potential and cell surface marker. At 4 weeks after surgery, the BV/TV value of the De-BMSCs group 0.36±0.01 was significantly higher than that of the control group 0.24±0.03 and BMSCs group 0.30±0.02 (all P<0.05), and the maximum load 40.34±1.19 N and stiffness 20.67±2.14 N/mm were significantly higher than those in the control group 14.88±2.74N, 8.67±2.19 N/mm and the BMSCs group 26.31±1.76 N, 13.81±2.14 N/mm (all P<0.05). At 12 weeks after surgery, the BV/TV value of the De-BMSCs transplantation group 0.47±0.02 was significantly higher than that of the control group 0.30±0.02 and the BMSCs group 0.35±0.03 (all P<0.05), and the maximum load 64.46±6.69 N and stiffness 25.18±3.11 N/mm were significantly higher than those in the control group 41.01±6.12 N, 11.59±2.54 N/mm and the BMSCs group 48.21±4.12 N, 15.89±2.94 N/mm (all P<0.05). During the osteogenic differentiation of De-BMSCs, the expressions of Nanog and NFATc1 were synergistically increased which promoted interaction of NFATc1 and Osterix ( P< 0.05), resulting in the increased expression of osteoblast marker genessuch as COL1A, OCN, OPN (all P< 0.05). Conclusion:De-BMSCs transplantation could promote bone formation at the tendon-bone interface after ACLR,Nanog/NFATc1/Osterix signaling pathway mediated the enhancement of the osteogenic differentiation effect of De-BMSCs.
9.Analysis of surveillance results of iodine deficiency disorders in Fuzhou City, Jiangxi Province from 2017 to 2019
Defu LI ; Jun SHANGGUAN ; Yuqi YU ; Quqin LU
Chinese Journal of Endemiology 2022;41(6):480-483
Objective:To analyze the surveillance results of iodine deficiency disorders in Fuzhou City, Jiangxi Province, so as to master the iodine nutrition level of key population and evaluate the prevention and treatment effect of iodine deficiency disorders in the city.Methods:From 2017 to 2019, counties (districts) under the jurisdiction of Fuzhou City in Jiangxi Province were divided into five sampling areas (east, west, south, north, and central). A township was selected in each area, and a primary school was selected in each township. Forty children aged 8 to 10 were elected in each primary school. At the same time, 20 pregnant women were selected from each area. Home salt samples and urine samples of children and pregnant women were collected to determine the contents of salt iodine and urinary iodine, and the thyroid of children was examined by B-mode ultrasonography.Results:A total of 6 001 salt samples from children's homes were tested. The median iodine content of children's home salt samples was 24.60 mg/kg, the coverage rate of iodized salt reached 99.77% (5 987/6 001), and the edible rate of qualified iodized salt was 96.20% (5 773/6 001). A total of 3 000 salt samples from pregnant women's homes were tested. The median iodine content of pregnant women's home salt samples was 24.81 mg/kg, the coverage rate of iodized salt reached 99.97% (2 999/3 000), and the edible rate of qualified iodized salt was 96.97% (2 909/3 000). A total of 6 001 children's urine samples were tested, and the median urinary iodine was 172.23 μg/L. A total of 3 000 pregnant women's urine samples were tested, and the median urinary iodine was 178.35 μg/L. The rate of goiter in children was 1.00% (8/800) in 2017, 1.33% (8/600) in 2018, and 1.12% (9/800) in 2019.Conclusion:The iodine nutrition level of children and pregnant women in Fuzhou City of Jiangxi Province is suitable and meets the requirements of iodine deficiency disorders elimination standard.
10.Status of iodine nutrition in pregnant women in Jiangxi Province in 2019
Jun SHANGGUAN ; Mingqun ZHU ; Binghua ZHOU ; Zhanqiu MAO ; Zifen LI ; Guai TANG
Chinese Journal of Endemiology 2021;40(7):551-553
Objective:To study the iodine nutritional status of pregnant women in Jiangxi Province, and to provide basis for iodine supplementation scientifically.Methods:In 2019, 100 counties (cities, districts, referred to as counties) of 11 cities in Jiangxi Province were selected by systematic sampling. Each county was divided into five sections according to five directions: east, west, south, north and middle. One township (street) was taken in each section, and 20 pregnant women (balanced early, middle and late pregnancy) were taken from each township (street) to detect their family salt iodine and urinary iodine levels in order to compare the levels of salt iodine and urinary iodine of different cities and the distribution of urinary iodine in different stages of pregnancy.Results:A total of 10 000 edible salt samples were collected from the families of pregnant women, the median of salt iodine was 24.53 mg/kg, the consumption rate of qualified iodized salt was 97.05% (9 705/10 000), and the iodized salt coverage rate was 99.80% (9 980/10 000). There was no significant difference in the iodine content of edible salt of pregnant women in different cities ( H = 3.42, P > 0.05). A total of 10 000 urine samples were collected from pregnant women, the median of urinary iodine was 175.58 μg/L. There was a statistically significant difference in the urinary iodine content of pregnant women in different cities ( H = 28.80, P < 0.01). There was no statistically significant difference in urinary iodine distribution of pregnant women in different stages of pregnancy (χ 2 = 5.73, P > 0.05). Conclusion:The iodine nutritional status of pregnant women in Jiangxi Province is in a suitable state, but the distribution of iodine nutritional status of pregnant women in different regions is uneven, iodine nutritional status of pregnant women in key regions should be paid attention to.

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