1.Establishment of quantitative analysis model for quality control indexes of Farfarae Flos based on NIRS
Tao GENG ; Wenhui JIANG ; Jialun LIU ; Songping LAN ; Liuying WANG ; Peilin CHEN ; Hanjing YAN ; Shengguo JI
China Pharmacy 2024;35(9):1057-1063
OBJECTIVE To establish a quantitative analysis model for the contents of tussilagone, moisture, ethanol-soluble extract and total ash in Farfarae Flos based on near-infrared spectroscopy (NIRS), providing a new idea for the rapid quality evaluation of Farfarae Flos and its preparations. METHODS Referring to the 2020 edition of the Chinese Pharmacopoeia, the contents of the main quality control indexes tussilagone, moisture, ethanol-soluble extract and total ash in 130 batches of Farfarae Flos from 19 producing areas were determined by HPLC, drying method, hot dip method and ash assay, respectively. The NIRS data information of the medicinal herbs of Farfarae Flos was collected, and then NIRS combined with the partial least squares method was used to establish the individual quantitative analysis models of the above quality control indexes in the samples, and the predictive model of the NIRS content was obtained after sample validation with validation set. RESULTS The range for the contents of tussilagone, moisture, ethanol-soluble extract and total ash in 130 batches of Farfarae Flos were 0.051 4%-0.103 5%, 7.75%-10.93%, 20.17%-31.12%, and 7.68%-12.10%, respectively. The internal cross-validation coefficients of determination (R2) of the established models for the quantitative analysis of tussilagone, moisture, ethanol-soluble extract and total ash in Farfarae Flos were 0.985 8, 0.968 4, 0.973 4, 0.988 0, respectively; the root mean square errors of calibration (RMSEC) were 0.001 54, 0.187, 0.478, 0.127, respectively; the root mean square errors of prediction (RMSEP) were 0.001 81, 0.212, 0.543, 0.149, respectively; RMSEP/RMSEC were 1.175 3, 1.133 7, 1.136 0 and 1.173 2, respectively, which were all within a reasonable range (1<RMSEP/RMSEC≤1.2). The mean absolute errors between the true and model-predicted values of the above four quality control indexes in the validation set of samples were -0.000 36, 0.061 43, 0.144 00, and 0.010 43, respectively,and the mean predicted recoveries were 99.65%, 100.72%,100.66%, and 100.15%, respectively. CONCLUSIONS The established NIRS quantitative analysis model has high stability and reliable results, which can be used for the rapid batch prediction of the content of relevant quality control indexes in Farfarae Flos.
2.Beta-sitosterol improves cerebral ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress
Xingyun YUAN ; Fei WANG ; Wanhong CHEN ; Wenqiang LI ; Juanli ZHANG ; Qing LIU ; Jialun XIN ; Li YAO
Chinese Journal of Neuromedicine 2024;23(9):886-894
Objective:To reveal the effect of β-sitosterol on cerebral ischemia-reperfusion injury (CIRI) in rats and whether its mechanism is related to endoplasmic reticulum stress (ERS).Methods:Fifty-three CIRI rats (CIRI models established by modified Longa method) were randomly divided into model group ( n=14), β-sitosterol low-dose group ( n=13), β-sitosterol medium-dose group ( n=13) and β-sitosterol high-dose group ( n=13); 12 rats underwent the same operation without blocking the middle cerebral artery were selected as sham-operated group. Rats in the sham-operated group and model group were given intragastric administration of 1 mL 5 g/L sodium carboxymethyl cellulose daily. Rats in the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group were given intragastric administration of 1 mL β-sitosterol at 10, 20 and 40 mg/kg/d (dissolved in 5 g/L sodium carboxymethyl cellulose), respectively, for 14 consecutive d. Neurological function was evaluated according to Zea Longa 5 method. Rats were sacrificed and brain tissues were collected. Volume of cerebral infarction was measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Brain injury and neuronal apoptosis were evaluated by HE staining, Nissl staining and TUNEL. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) contents were detected by water-soluble tetrazolium 1 (WST-1) method, colorimetric method or thiobarbituric acid (TBA) method, respectively. The mRNA and protein expression levels of protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme-1 (IRE-1), activated transcription factor-6 (ATF-6), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and Caspase-12 in the brain tissues were detected by qRT-PCR or Western blotting. Results:Compared with the sham-operated group, the model group had significantly increased neurological function score, cerebral infarction volume and TUNEL positive rate, decreased SOD and GSH-Px content, increased MDA content, and increased mRNA and protein expressions of PERK, IRE-1, ATF-6, GRP78, CHOP and Caspase-12 ( P<0.05). Compared with the model group, the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group had significantly decreased neurological function score, cerebral infarction volume, and TUNEL positive rate, increased SOD and GSH-Px content, and decreased MDA content ( P<0.05); the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group had significantly decreased mRNA and protein PERK expressions (mRNA: 2.17±0.17, 1.79±0.07 and 1.33±0.07; protein: 5.11±0.52, 2.91±0.26 and 1.98±0.17), IRE-1 expressions (mRNA: 1.75±0.18, 1.65±0.08 and 1.32±0.08; protein: 5.00±0.31, 4.05±0.27 and 1.98±0.14), ATF-6 expressions (mRNA: 2.24±0.12, 1.77±0.14 and 1.37±0.13; protein: 4.93±0.45, 4.04±0.30 and 3.10±0.20), GRP78 expressions (mRNA: 2.67±0.16, 2.11±0.16 and 1.69±0.11; protein: 5.02±0.38, 2.97±0.26 and 2.05±0.22), CHOP expressions (mRNA: 2.01±0.16, 1.70±0.19 and 1.40±0.10; protein: 4.92±0.39, 4.02±0.27 and 3.08±0.22) and Caspase-12 expressions (mRNA: 1.85±0.09, 1.61±0.09 and 1.30±0.09; protein: 3.03±0.20, 2.19±0.11 and 1.82±0.11) compared with the model group (mRNA: 2.99±0.28, 2.27±0.12, 2.57±0.21, 3.46±0.20, 2.50±0.23 and 2.35±0.16; protein: 6.98±0.48, 6.03±0.58, 5.98±0.63, 7.10±0.45, 6.00±0.53 and 5.02±0.43, P<0.05). Conclusion:β-sitosterol attenuates CIRI in rats, whose mechanism may be related to inhibition of ERS signal pathway.
3.Construction and application of hospital multi-source heterogeneous data fusion platform
Yang LIU ; Xia WEN ; Yaxi KANG ; Weicong CHEN ; Ziren SU ; Jialun LIN
Chinese Journal of Hospital Administration 2024;40(4):305-309
Building a multi-source heterogeneous data fusion platform for clinical data centers has become a common consensus in the medical information industry. The data fusion platform built by a certain hospital consisted of five parts: data acquisition module, data processing module, data comparison and repair module, data subscription and application module, and data fusion management platform. Data quality check was conducted on data scattered across the hospital′s operational systems with different structures and types, diverse patterns and states, different sizes and versions. The platform could handle duplicate and redundant metadata, collect, transform, process, distribute, and load data as needed, and maintain data consistency through comparison and repair. This platform is capable of automatically capturing, analyzing, governing, and integrating different types of data across databases, operating systems, and hardware environments, meeting diverse medical data application needs, and supporting the high-quality development of intelligent hospitals
4.Progress of Chimeric Antigen Receptor Gene Modified-T Cell Immunotherapy for Thoracic Malignancies
Fukun CHEN ; Nana CHEN ; Zhiyong DENG ; Juan LYU ; Wenjing QIN ; Jialun ZHU
Cancer Research on Prevention and Treatment 2023;50(10):1010-1014
With a deepened understanding of the pathophysiology and pathogenesis of thoracic malignancies, the treatment has been transited from traditional treatment on the basis of surgery, radiotherapy, and chemotherapy to individualized and precise targeted therapy and immunotherapy. As an antitumor immunotherapy, chimeric antigen receptor gene-modified T (CAR-T) cells have been approved by the FDA for the treatment of hematological malignancies in five CAR-T products. They have also achieved good therapeutic effects in solid tumors. However, significant challenges remain in the clinical application of CAR-T cell immunotherapy in thoracic malignancies. In this review, the latest research progress of CAR-T cell immunotherapy in the treatment of thoracic malignancies were summarized, including the basic characteristics of CAR-T cells, the popular target antigens, and the existing problems and challenges, to provide new ideas and strategies for clinical immunotherapy of thoracic malignancies.
5.Acute external otitis after hyaluronic acid injection : a case report
Dong WANG ; Yang LIU ; Guangyu CHEN ; Jialun LI ; Yajie ZHANG
Chinese Journal of Plastic Surgery 2023;39(10):1106-1109
A 23-year-old female patient underwent hyaluronic acid injection to treat bilateral decumbent ear deformity in April 2023 in another hospital. She developed dizziness, nausea, vomiting, intense pain in the left ear canal with bleeding fluid outflow, and significant hearing loss in the left ear 12 h after surgery. She was admitted to Jinan Meiao Plastic Surgery Hospital for specialized medical examination and electronic endoscopy after admission. The patient was diagnosed as acute external otitis after hyaluronic acid injection. The patient’s external ear canal was irrigated with drugs, injected with hyaluronidase solution, followed by symptomatic treatment. After 7 days, the patient’s symptoms disappeared, and her hearing was recovered. In clinical application of hyaluronic acid injection, plastic surgeons should strictly follow indications, master the knowledge of hyaluronic acid preparation and the anatomical structure of the injection site, as well as improve injection techniques, to avoid complications. Also, plastic surgeons should be familiar with the emergency treatment of various complications.
6.Acute external otitis after hyaluronic acid injection : a case report
Dong WANG ; Yang LIU ; Guangyu CHEN ; Jialun LI ; Yajie ZHANG
Chinese Journal of Plastic Surgery 2023;39(10):1106-1109
A 23-year-old female patient underwent hyaluronic acid injection to treat bilateral decumbent ear deformity in April 2023 in another hospital. She developed dizziness, nausea, vomiting, intense pain in the left ear canal with bleeding fluid outflow, and significant hearing loss in the left ear 12 h after surgery. She was admitted to Jinan Meiao Plastic Surgery Hospital for specialized medical examination and electronic endoscopy after admission. The patient was diagnosed as acute external otitis after hyaluronic acid injection. The patient’s external ear canal was irrigated with drugs, injected with hyaluronidase solution, followed by symptomatic treatment. After 7 days, the patient’s symptoms disappeared, and her hearing was recovered. In clinical application of hyaluronic acid injection, plastic surgeons should strictly follow indications, master the knowledge of hyaluronic acid preparation and the anatomical structure of the injection site, as well as improve injection techniques, to avoid complications. Also, plastic surgeons should be familiar with the emergency treatment of various complications.
7.Establishment of characteristic chromatogram and content determination of 4 index components in Jianpi yifei biyan prescription standard decoction
Xin WAN ; Detang LI ; Lijuan ZHANG ; Meirong YI ; He ZHU ; Jialun HE ; Jie CHEN ; Hongmei TANG ; Zhenwen QIU
China Pharmacy 2022;33(16):1980-1985
OBJECTIVE To establish HPLC characteristic chro matogram of Jianpi yifei biyan prescription standard decoction , to select the quality control index components and determine their contents. METHODS HPLC method combined with Similarity Evaluation System of TCM Chromatographic Fingerprint (2004 edition)were used to establish the characteristic chromatogram of 10 batches of Jianpi yifei biyan prescription standard decoction ;the similarity evaluation and common peaks identification were also carried out. Using common peak area of characteristic chromatogram as variables ,SPSS 26.0 software and SIMCA 14.1 software were used to perfor m cluster analysis (CA),principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA);differential components with variable important i n pro jection(VIP)value greater than 1.5 were screened;the contents of cimifugin and differential components were determined by the same method. RESULTS A total of 24 common characteristic peaks were identified , and the similarities of 10 batches of samples were higher than 0.960;eight characteristic peaks were identified by comparison with reference substance. CA and PCA results revealed that the samples were classified into 3 categories.OPLS-DA analysis showed that 3 components with VIP value greater than 1.5, which were prim-O-glucosylcimifugin (peak 2),calycosin 7-O-β-D-glucopyranoside (peak 4) and 5-O-methylvisammioside (peak 6) in descending order. The linear ranges of prim- O- glucosylcimifugin,calycosin 7-O-β-D-glucopyranoside,cimifugin and 5-O-methylvisammioside were 0.010 7-0.213 0,0.007 8- 0.156 0,0.008 0-0.160 0,0.009 8-0.195 0 μg(r>0.999),respectively. RSD values of precision ,repeatability and stability tests (24 h) were all less than 2%. Average recoveries were 105.98%(RSD=1.75%,n=6),98.06%(RSD=3.87%,n=6),96.38%(RSD= 4.03% ,n=6) and 104.17%(RSD=1.27% ,n=6). The contents of the above 4 components in 10 batches of samples were 12.12-18.87,3.86-6.40,3.10-4.27 and 11.17-15.79 μ g/mL,respectively. CONCLUSIONS The established HPLC characteristic chromatographic method is stable and feasible ,it can be used for the quality control of Jianpi yifei biyan prescription standard decoction. Prim- O-glucosylcimifugin,calycosin 7-O-β-D-glucopyranoside,cimifugin and 5-O-methylvisammioside can be used as the index components for quality control of the standard decoction.
8.BRD4 inhibitor specifically inhibits the development of wild-type Kras differentiated thyroid carcinoma by regulating BRD4/miR-106b-5p/P21 axis
Zhiping FENG ; Chuanzhou YANG ; Ting CHEN ; Jialun ZHU ; Chao LIU ; Juan LYU ; Jianmei LU ; Zhiyong DENG
Journal of International Oncology 2021;48(8):463-472
Objective:To explore the influence of bromodomain-containing protein 4 (BRD4) inhibitor on wild-type Kras differentiated thyroid carcinoma (DTC) and its mechanism.Methods:The DTC cell line Kras WT TPC-1 was selected and the mutant Kras G12D TPC-1 cells were constructed. CCK-8 assay was used to detect the effect of BRD4 inhibitor JQ-1 on the proliferation activity of Kras WT TPC-1 cells. Kras WT TPC-1 cells were treated with 0.2 μmol/L JQ-1 (JQ-1 group), and a negative control group (NC group) was set. Transwell invasion assay and flow cytometry were used to detect the effect of JQ-1 on the invasion and apoptosis of Kras WT TPC-1 cells. The effect of JQ-1 on the expressions of BRD4, miR-106b-5p and P21, and the effect of P21 inhibitor UC2288 on the expressions of P21 and BRD4 were detected. Kras WT TPC-1 cells were divided into JQ-1+ NC-OE group, JQ-1+ p21-OE group (overexpression of p21) and JQ-1+ p21-OE+ miR-106b-5p mimic group (overexpression of p21 and miR-106b-5 at the same time), and the proliferation, invasion and apoptosis of cells in each group were detected. TPC-1 cells were divided into Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, and the cell proliferation, invasion and apoptosis of each group were detected. Results:JQ-1 inhibited the proliferation activity of Kras WT TPC-1 cells in a dose-dependent and time-dependent manner. In the NC group and JQ-1 group, the numbers of cell invasion were 124.67±9.61 and 82.67±8.02, and the apoptosis rates were (5.91±0.34)% and (10.33±1.10)%, respectively, with statistically significant differences ( t=5.812, P=0.004; t=6.653, P=0.003). JQ-1 significantly inhibited the expressions of BRD4 and miR-106b-5p, and promoted the expression of P21 in Kras WT TPC-1 cells. UC2288 significantly inhibited P21 expression, but had no significant effect on BRD4 expression. In the JQ-1+ NC-OE group, JQ-1+ p21-OE group and JQ-1+ p21-OE+ miR-106b-5p mimic group, the proliferation activities at 24 h of Kras WT TPC-1 cells was 0.46±0.03, 0.35±0.04 and 0.44±0.03 ( F=8.720, P=0.017), and the proliferation activity of JQ-1+ p21-OE group was significantly lower than that of the JQ-1+ NC-OE group ( P<0.05). The numbers of cell invasion in the three groups were 83.00±9.17, 56.67±6.03 and 79.67±10.07 ( F=8.347, P=0.018), and the number of cell invasion in the JQ-1+ p21-OE group was significantly lower than that in the JQ-1+ NC-OE group ( P=0.009). The apoptosis rates of the three groups were (10.00±0.49)%, (15.39±1.14)% and (10.32±0.80)% ( F=37.764, P<0.001), and the apoptosis rate of the JQ-1+ p21-OE group was significantly higher than that in the JQ-1+ NC-OE group ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between JQ-1+ p21-OE+ miR-106b-5p mimic group and JQ-1+ NC-OE group (all P>0.05). In Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, the cell proliferation activities at 24 h were 0.50±0.05, 0.39±0.04, 0.68±0.08 and 0.64±0.05 ( F=17.776, P<0.001). Compared with the Kras WT group, cell proliferation activity in the Kras WT+ JQ-1 group was significantly decreased, while that in the Kras G12D group was significantly increased (both P<0.05). The numbers of cell invasion in the four groups were 129.33±11.50, 86.00±9.54, 161.67±13.01 and 146.33±13.20 ( F=22.598, P<0.001). Compared with the Kras WT group, the number of cell invasion in the Kras WT+ JQ-1 group was significantly decreased ( P=0.002), and that in the Kras G12D group was significantly increased ( P=0.010). The apoptosis rates in the four groups were (6.17±0.50)%, (10.42±0.73)%, (3.43±0.47)% and (3.41±0.32)% ( F=119.170, P<0.001). Compared with the Kras WT group, the apoptosis rate in the Kras WT+ JQ-1 group was significantly increased ( P<0.001), and that in the Kras G12D group was significantly decreased ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between Kras G12D+ JQ-1 group and Kras G12D group (all P>0.05). Conclusion:BRD4 inhibitor can specifically inhibit the development of wild-type Kras DTC via regulating the molecular axis of BRD4/miR-106b-5p/P21, but has no significant effect on the proliferation, invasion and apoptosis of mutant Kras DTC tumor cells.
9.Correlation between KRAS genemutationandDTC resistance to 131I radiotherapy and prognosis
FENG Zhiping ; CHEN Fukun ; YANG Chuanzhou ; CHEN Ting ; ZHU Jialun ; LIU Chao ; LV Juan ; LU Jianmei ; DENG Zhiyong
Chinese Journal of Cancer Biotherapy 2019;26(2):213-219
Objective: To investigate the correlation between KRAS gene mutation and differentiated thyroid carcinoma (DTC) treatment effect and prognosis, and to explore the mechanism. Methods: Clinical tissue samples from DTC patients undergoing 131I Radiotherapy were collected. Then single strand conformation polymorphism analysis of polymerase chain reaction products (PCRC-SSCP) was used to detect KRAS mutation rate in thyroid cancer patients of different TNM stages; p21 protein expression level was detected by real-time quantitative polymerase chain reaction (qPCR) and western blotting. DTC cells were treated by sub-lethal dose of 131I Radiotherapy, and then CCK-8 assay, transwell assay and flow cytometry (FCM) were used to evaluate the changes of cells viability. Animal models were then constructed for verification. Results: The results showed that KRAS gene mutants were increased in 131I-resistant DTC patients; KRAS gene mutation suppressed p21 protein expression and was associated with clinical stage and poor prognosis. In vivo and in vitro experiments proved that sub-lethal dose of 131I increased KRAS gene mutation rate, suppressed p21 expression level, and caused 131I radiotherapy resistance. Reversely, over-expression of KRAS gene could significantly increase p21 expression, and inhibit tumor proliferation and metastasis. Conclusion: KRAS gene mutations were associated with DTC TNM stages and 131I resistance in DTC patients. Sub-lethal dose of 131I treatment could improve 131I resistance in DTC cells line, inversely, over-expressed KRAS gene could increase the sensitivity to 131I radiotherapy in DTC patients.
10. The limitation of transthoracic echocardiography in diagnosing partial anomalous pulmonary venous drainage
Jing ZHANG ; Yan GAO ; Jialun YANG ; Weida CHEN ; Guoying HUANG ; Xiaojing MA
Chinese Journal of Pediatrics 2017;55(5):360-363
Objective:
To improve the diagnostic accuracy of transthoracic echocardiography (TTE) by analyzing its limitations in diagnosing partial anomalous pulmonary venous drainage (PAPVD).
Method:
This was a retrospective analysis of PAPVD patients seen at the Children′s Hospital of Fudan University from October 1 2006 to October 1 2016. The echocardiographic data were compared to findings on multi-slice spiral CT (MSCT), cardiac catheterization or surgery. The echocardiography machines used were Philip IE33, GE Vivid 7 and Vivid i with frequency ranging from 5.0 MHz to 7.5 MHz. The cardiac structure was analyzed according to Van Praagh segments.
Result:
A total of 43 cases of PAPVD were enrolled, male∶ female ratio 20∶23 with average age (27.9±21.4) months. Among them, 3 cases were simple PAPVD and 40 cases had other associated congenital heart diseases. TTE was successful in diagnosing 29 cases (67%) while 14 cases were missed. The diagnostic rate for right pulmonary vein drainage into superior vena cava, right atrium, inferior vena cava were 5/10, 17/20, and 3/5 respectively while left pulmonary vein drainage into left innominate vein was only 1/4. Added TTE images to re-exam the 9 of the 14 missed cases, 5 cases of abnormal drainage from right superior pulmonary vein were diagnosed, while 4 cases of drainage from right lower or left pulmonary vein were only picked up by indirect signs.
Conclusion
The distance of the pulmonary veins from the routine ultrasound view and the possibility of branch number variation may limit the accuracy of TTE in diagnosing PAPVD, especially for drainage from right lower and left pulmonary vein. But TTE is still the preferred diagnostic method. The diagnostic rate could be increased by paying special attention to non-routine views including the suprasternal fossa, the right parasternal and subcostal area.

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