1.Effect of tubastatin A on pyroptosis during brain injury after cardiac arrest and resuscitation in swine
Qijiang CHEN ; Jiefeng XU ; Caimu WANG ; Xinjie WU ; Xue ZHAO
Chinese Journal of Anesthesiology 2024;44(3):344-348
Objective:To evaluate the effect of tubastatin A (TubA) on pyroptosis during brain injury after cardiac arrest and resuscitation in swine.Methods:Twenty-two conventional male white swine, weighing 34-39 kg, aged 4-6 months, were divided into 3 groups using a random number table: sham operation group (group S, n=6), cardiac arrest-cardiopulmonary resuscitation (CA-CPR) group ( n=8) and CA-CPR+ TubA group ( n=8). The swine model of CA-CPR was established by 9 min of cardiac arrest and 6 min of cardiopulmonary resuscitation in CA-CPR group and CA-CPR+ TubA group. TubA 4.5 mg/kg (in 50 ml of normal saline) was infused over 1 h via the femoral vein starting from 5 min after resuscitation in CA-CPR+ TubA group. Before developing the model and at 1, 2, 4 and 24 h after resuscitation (T 0-4), blood samples were collected from the femoral vein for determination of the concentrations of neuron specific enolase (NSE) and S100β protein in serum (by enzyme-linked immunosorbent assay). Neurological deficit score (NDS) was evaluated at T 4. The animals were then sacrificed, and their brain cortex tissues were harvested to measure the expression of histone deacetylase 6 (HDAC6), caspase-3, cleaved caspase-3, gasdermin E (GSDME) and GSDME N-terminal (N-GSDME) (by Western blot) and contents of high mobility group box 1 (HMGB1), interleukin-1β (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the serum concentrations of NSE and S100β were significantly increased at T 1-4, NDS was increased at T 4, the expression of HDAC6, caspase-3, cleaved caspase-3, GSDME and N-GSDME in brain cortex was up-regulated, and the contents of HMGB1, IL-1β and IL-18 were increased in CA-CPR and CA-CPR+ TubA groups ( P<0.05). Compared with group CA-CPR, the serum concentrations of NSE and S100β were significantly decreased at T 3, 4, NDS was decreased at T 4, the expression of HDAC6, caspase-3, cleaved caspase-3, GSDME and N-GSDME in brain cortex was down-regulated, and the contents of HMGB1, IL-1β and IL-18 were decreased in group CA-CPR+ TubA ( P<0.05). Conclusions:The mechanism by which TubA alleviates brain injury after cardiac arrest and resuscitation may be related to inhibition of pyroptosis in swine.
2.Construction of a risk prediction model for increasing body mass index during treatment in breast cancer patients
Qing WANG ; Xinjie JIA ; Xue WU ; Miao WANG ; Xin HE
Chinese Journal of Practical Nursing 2024;40(31):2422-2429
Objective:To investigate the independent influencing factors of body mass index (BMI) growth risk during breast cancer treatment and establish a predictive model, and validate its predictive efficacy.Methods:A retrospective cohort study was conducted by a convenience sampling method. 306 eligible breast cancer patients underwent follow-up at the Tianjin Medical University Cancer Hospital between January and May 2023 were selected as the modeling group. The BMI changes of the modeling group patients were monitored during the study period. Patients with BMI changed < ± 0.5 kg/m 2 were classified as the stable group, while those with BMI changed ≥ 0.5 kg/m 2 were classified as the growth group. Factor analysis was conducted, and a predictive model was established. The fitting effect was verified by the Hosmer-Lemeshow test, and the receiver operating characteristic (ROC) curve was drawn to verify the model′s predictive ability. 110 eligible breast cancer patients underwent follow-up at the Tianjin Medical University Cancer Hospital between June and August 2023 were selected as the validation group to verify the predictive effect of the model. Results:The age of the modeling group patients was (48.89 ± 7.78) years, BMI was (25.53 ± 1.39) kg/m 2 and the age of the validation group patients was (50.18 ± 7.70) years, BMI was(24.31 ± 0.86) kg/m 2, both groups were female, there were no significant differences between the two groups (all P>0.05). Axillary lymph node dissection ( OR=4.196, 95% CI 3.512-9.158), chemotherapy duration ( OR=2.002, 95% CI 1.001-3.003), premenopausal status ( OR=3.257, 95% CI 1.244-3.733), low health behavior capacity ( OR=5.977, 95% CI 2.878-7.893), and low physical activity ( OR=3.755, 95% CI 1.244-11.733) were identified as independent influencing factors of BMI change during breast cancer treatment (all P<0.05). The predictive model was P=0.915, with the ROC curve area of 0.950, a J-index of 0.785, a sensitivity of 0.971, and a specificity of 0.814. Internal and external validation of the model in the validation group revealed a sensitivity of 0.858, a specificity of 0.887, and an accuracy of 97.3%. Conclusion:The predictive model exhibited excellent performance and can serve as a valuable tool for formulating nursing intervention strategies to maintain the BMI stability of breast cancer patients during treatment.
3.Application of mixed reality in mandibular repair and reconstruction
Xinjie YANG ; Zihui YANG ; Huan LI ; Chaojie WANYAN ; Jun WANG ; Xiangming YANG ; Zhongming WU ; Weiqi WANG ; Jianhua WEI
Chinese Journal of Medical Aesthetics and Cosmetology 2023;29(2):81-84
Objective:To explore the effect of mixed reality (MR) application in the reconstruction of mandibular defects.Methods:Eighteen patients with mandibular defects were enrolled in this study, including 10 male patients and 8 female patients, whose age ranged from 27 to 45 years, and the mean age was 35.4 years. All the patients were from the Stomatological Hospital of the Fourth Military Medical University, during October 2019 to May 2021. Fibular flaps were used for the reconstruction of the mandibular defects. The patients were randomly divided into three groups, six in each group. In group one, MR-guided mandibular defect repair and reconstruction technique was used. In group two, 3D printed guide-assisted mandibular defect repair and reconstruction technique was used, and in the control group, traditional jaw defect repair and reconstruction technique was used. All the procedures were performed by the same team. Cone beam computed tomography (CBCT) was used for analysis of surgical accuracy, and questionnaires were used to evaluate the outcome of medical communication, occlusal relationship, appearance restoration, and medical experience satisfaction.Results:The mean surgical errors in the group one and group two were (1.75±0.44) mm and (1.81±0.16) mm respectively, which were both significantly lower than that in the control group (3.05±0.83) mm ( tMR=3.38, t3D=3.56, P<0.01). The medical communication (4.60±0.35, 4.52±0.28, tMR=2.90, t3D=2.77, P<0.05), occlusal relationship (4.17±0.32, 4.28±0.39, tMR=3.07, t3D=3.29, P<0.05), and medical experience satisfaction scores (4.26±0.45, 4.25±0.67, tMR=2.50, t3D=2.26, P<0.05) in the experimental groups were significantly higher than those in the control group (4.02±0.34, 3.58±0.33, 3.56±0.32, respectively). There was no significant difference in the satisfaction of appearance recovery among all the groups ( P>0.05). Conclusions:MR-guided mandibular repair and reconstruction surgery has high accuracy and is also beneficial to the recovery of occlusal relationship and medical communication.
4.Effects of thigh perforator flap on repair of oral and maxillofacial head and neck defects
Xiangming YANG ; Zhongming WU ; Fengrui ZHANG ; Lizhi XU ; Siyuan FAN ; Huan LI ; Zhenyan ZHAO ; Xinjie YANG ; Jianhua WEI
Chinese Journal of Medical Aesthetics and Cosmetology 2023;29(2):85-89
Objective:To investigate the clinical experience of different types of femoral perforator flaps in the reconstruction of oral and maxillofacial head and neck defects.Methods:From January 2018 to January 2021, 573 patients with oral and maxillofacial head and neck defects reconstructed by femoral perforator flap were collected in the Department of Maxillofacial Oncology, the Third Affiliated Hospital of Air Force Military Medical University (age range of 21-76 years, with a male to female ratio of 1.23∶1). According to the type of perforator flap, the patients were divided into ALT group, AMT group, TFL flap group and free muscle flap group. The incidence of postoperative complications, wound healing time and drainage volume in femoral area were compared among the 4 groups.Results:The ALT flap was used in 527 cases: 22 flaps had vascular crisis, 14 flaps had infection, 8 flaps had necrosis, 519 flaps survived; the mean healing time of the wound was (14.50±3.19) days, and the mean drainage volume was (49.9±21.3) ml. 28 cases were repaired with AMT flap: 2 flaps had vascular crisis and 1 had infection. All the flaps survived; the mean healing time of the wound was (14.18±2.75) days, and the mean drainage volume was (50.3±23.0) ml. 11 cases were repaired by TFL flap: 1 flap had vascular crisis and 1 had infection. All the flaps survived. The mean healing time of the wound was (14.09±2.66) days, and the mean drainage volume was (54.1±25.0) ml. 7 cases were repaired by free muscle flap survived without vascular crisis, infection and other postoperative complications; the mean healing time of the wound was 14.14±1.86, and the mean postoperative drainage volume was (49.9±21.1) ml. There was no significant difference in complication rate (flap necrosis, vascular crisis, infection, etc.) and repair effect among 573 patients with different flap types. The postoperative follow-up was conducted for 6-24 months, and the donor area was smooth and good in appearance, without obvious scar or functional influence. The repair effect of the affected area was satisfactory.Conclusions:Although there is a certain proportion of perforator vessel variation in the femoral perforator flap, the flap can be designed freely according to different types of variation. The thigh perforator flap has an essential application value in the repair of oral and maxillofacial head and neck defects.
5.Protective role and mechanism of tubastatin A on renal and intestinal injuries after cardiopulmonary resuscitation in swine.
Xinjie WU ; Xue ZHAO ; Qijiang CHEN ; Ying LIU ; Jiefeng XU ; Guangju ZHOU ; Mao ZHANG
Chinese Critical Care Medicine 2023;35(4):398-403
OBJECTIVE:
To investigate the protective effect and potential mechanism of tubastatin A (TubA), a specific inhibitor of histone deacetylase 6 (HDAC6), on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in swine.
METHODS:
Twenty-five healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 10) and TubA intervention group (n = 9) using a random number table. The porcine model of CPR was reproduced by 9-minute cardiac arrest induced by electrical stimulation via right ventricle followed by 6-minute CPR. The animals in the Sham group only underwent the regular operation including endotracheal intubation, catheterization, and anesthetic monitoring. At 5 minutes after successful resuscitation, a dose of 4.5 mg/kg of TubA was infused via the femoral vein within 1 hour in the TubA intervention group. The same volume of normal saline was infused in the Sham and CPR model groups. Venous samples were collected before modeling and 1, 2, 4, 24 hours after resuscitation, and the levels of serum creatinine (SCr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) in serum were determined by enzyme-linked immunoadsordent assay (ELISA). At 24 hours after resuscitation, the upper pole of left kidney and terminal ileum were harvested to detect cell apoptosis by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and the expression levels of receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) were detected by Western blotting.
RESULTS:
After resuscitation, renal dysfunction and intestinal mucous injury were observed in the CPR model and TubA intervention groups when compared with the Sham group, which was indicated by significantly increased levels of SCr, BUN, I-FABP and DAO in serum. However, the serum levels of SCr and DAO starting 1 hour after resuscitation, the serum levels of BUN starting 2 hours after resuscitation, and the serum levels of I-FABP starting 4 hours after resuscitation were significantly decreased in the TubA intervention group when compared with the CPR model group [1-hour SCr (μmol/L): 87±6 vs. 122±7, 1-hour DAO (kU/L): 8.1±1.2 vs. 10.3±0.8, 2-hour BUN (mmol/L): 12.3±1.2 vs. 14.7±1.3, 4-hour I-FABP (ng/L): 661±39 vs. 751±38, all P < 0.05]. The detection of tissue samples indicated that cell apoptosis and necroptosis in the kidney and intestine at 24 hours after resuscitation were significantly greater in the CPR model and TubA intervention groups when compared with the Sham group, which were indicated by significantly increased apoptotic index and markedly elevated expression levels of RIP3 and MLKL. Nevertheless, compared with the CPR model group, renal and intestinal apoptotic indexes at 24 hours after resuscitation in the TubA intervention group were significantly decreased [renal apoptosis index: (21.4±4.6)% vs. (55.2±9.5)%, intestinal apoptosis index: (21.3±4.5)% vs. (50.9±7.0)%, both P < 0.05], and the expression levels of RIP3 and MLKL were significantly reduced [renal tissue: RIP3 protein (RIP3/GAPDH) was 1.11±0.07 vs. 1.39±0.17, MLKL protein (MLKL/GAPDH) was 1.20±0.14 vs. 1.51±0.26; intestinal tissue: RIP3 protein (RIP3/GAPDH) was 1.24±0.18 vs. 1.69±0.28, MLKL protein (MLKL/GAPDH) was 1.38±0.15 vs. 1.80±0.26, all P < 0.05].
CONCLUSIONS
TubA has the protective effect on alleviating post-resuscitation renal dysfunction and intestinal mucous injury, and its mechanism may be related to inhibition of cell apoptosis and necroptosis.
Male
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Animals
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Swine
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Abdominal Injuries
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Apoptosis
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Cardiopulmonary Resuscitation
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Kidney Diseases
6.LRRK2G2019S mutation induced microglia activation after iron removal by inhibiting autophagy associated proteins
Zheng LIU ; Zijian ZHENG ; Xinjie LIU ; Cheng XUE ; Xiao WU ; Xinran ZHANG ; Jianwei LI ; Lixuan LU ; Guohui LU
Chinese Journal of Neuromedicine 2023;22(11):1098-1110
Objective:To investigate the effect of LRRK2G2019S mutation on activation of microglia after iron deprivation and its mechanism.Methods:(1) Microglia were differentiated from human induced pluripotent stem cells (IPSC) with the help of hematopoietic progenitor cells (HPC) and identified by immunofluorescent staining, and α-synuclein (α-syn) A53T mutant protein was obtained by protein purification technology. (2) Microglia were divided into control group, α-syn group, α-syn+ deferoxamine (DFO) group; phosphate buffer solution (PBS), 1 μmol/L purified α-syn A53T mutant protein, 1 μmol/L purified α-syn A53T mutant protein+30 mmol/L DFO were given respectively for 24 h. Fe 2+ concentration was detected by colorimetry, Rab35 protein expression was detected by Western blotting, intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and interleukin-6 ( IL-6), tumor necrosis factor-α ( TNF-α) and transforming growth factor-β ( TGF-β) mRNA expressions were detected by real time-PCR (RT-PCR); microglia culture supernatant (MCS) in the 3 groups were transfered to SH-SY5Y cells, and SH-SY5Y cell apoptosis was detected by flow cytometry. (3) Bidirectional DNA sequencing was used to detect leucine rich repeat kinase 2 ( LRRK2) gene mutations in microglia treated with 1 μmol/L purified α-syn A53T mutant protein. Microglia were divided into control group, α-syn group and α-syn+GSK3357679A group, and treated with corresponding drugs for 24 h, respectively (LRRK2 inhibitor GSK3357679A concentration: 10 nmol/L), and LRRK2 protein expression was detected by Western blotting; microglia were divided into control group, α-syn group, α-syn+GSK3357679A, and α-syn+GSK3357679A+DFO group, and treated with corresponding drugs for 24 h, Rab35 protein expression was detected by Western blotting, intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (4) Microglia were divided into control group, α-syn group, α-syn+rapamycin (RAPA) group, and treated with corresponding drugs for 24 h (concentration of autophagy inducer RAPA: 50 nmol/L); protein expressions of Rab35, P62 and microtubule-associated protein light chain 3 II (LC3II) were detected by Western blotting; intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (5) Microglia were divided into control group, α-syn group, and α-syn+Rab35 group, and treated with corresponding drugs for 24 h (concentration of Rab35 overexpressed plasmids: 1 μg/mL); Rab35, P62, and LC3II protein expressions were detected by Western blotting; ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. Results:(1) Immunofluorescent staining showed negative neuronal nuclei (NeuN) expression and positive ionized calcium-binding adapter molecule 1 (Iba1) expression in microglia, and high LRRK2 expression; PcDNA3.1-SNCA-A53T expression plasmid was constructed and α-syn A53T mutant protein was purified. (2) The Fe 2+ concentration in α-syn group was significantly higher than that in control group, and the Fe 2+ concentration in α-syn+DFO group was significantly lower than that in α-syn group ( P<0.05); the Rab35 protein and TGF-β mRNA expressions in control group, α-syn group and α-syn+DFO group were decreased successively, while the IL-6 and TNF-α mRNA expressions were increased successively, with significant differences ( P<0.05); ROS level and SH-SY5Y cell apoptosis rate in control group, α-syn group, α-syn+DFO group were increased successively. (3) Bidirectional DNA sequencing showed that the LRRK2G2019S mutation in microglia was the most obvious after α-syn A53T mutant protein stimulation; compared with the control group, the α-syn group had significantly increased LRRK2 protein expression, while the α-syn+GSK3357679A group had significantly decreased LRRK2 protein expression compared with α-syn group ( P<0.05); compared with the control group, the α-syn group had significantly decreased Rab35 protein and TGF-β mRNA expressions, and statistically increased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+GSK3357679A group had significantly increased Rab35 protein and TGF-β mRNA expressions, and statistically decreased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn+GSK3357679A group, α-syn+GSK3357679A+DFO group had significantly increased IL-6 and TNF-α mRNA expressions, and significantly decreased Rab35 protein and TGF-β mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group, the α-syn+GSK3357679A group had lower ROS level than the α-syn group, and the α-syn+GSK3357679A+DFO group had higher ROS level than the α-syn+GSK3357679A group. (4) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly increased P62 protein, IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+RAPA group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); the α-syn group had higher ROS level than the control group and α-syn+RAPA group. (5) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and statistically increased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); compared with the α-syn group, the α-syn+Rab35 group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group and α-syn+Rab35 group. Conclusion:LRRK2G2019S can induce neuroinflammation by inhibiting Rab35-related autophagy under iron deprivation, and Rab35 is expected to be a key factor in intervening neuroinflammation.
7.Blood glucose fluctuation and risk factors in type 2 diabetic patients with asymptomatic hypoglycemia
Yonghong CAO ; Xudong YAO ; Erlan SHI ; Suwan ZHANG ; Shimei XING ; Shuai YE ; Xinjie SONG ; Rong ZHANG ; Zhenzhen WANG ; Wu DAI
Chinese Journal of Endocrinology and Metabolism 2022;38(12):1052-1056
Objective:To investigate the characteristics of blood glucose fluctuation and risk factors in type 2 diabetic patients with asymptomatic hypoglycemia.Methods:From September 2018 to July 2021, 342 patients with type 2 diabete mellitus who were hospitalized in the Department of Endocrinology of Hefei Hospital Affilitated to Anhui Medical University were enrolled for a retrospective study. The mean amplitude of glycemic excursions(MAGE), coefficient of variation (CV), 24 hour mean blood glucose level (MG), and time in range (TIR) were obtained by continuous glucose monitoring (CGM). According to the results of CGM and whether the patients have hypoglycemia symptoms, they were divided into three groups: no hypoglycemia group, symptomatic hypoglycemia group, and asymptomatic hypoglycemia group. The differences in blood glucose fluctuations were compared among the three groups. Multivariate logistic regression analysis was used to evaluate the risk factors in type 2 diabete mellitus patients with asymptomatic hypoglycemia. The predictive value of MAGE for asymptomatic hypoglycemia was analyzed by receiver operating characteristic (ROC) curve.Results:Compared with the non-hypoglycemia group, the TIR in asymptomatic hypoglycemia group was higher ( Z=-2.042, P=0.041). The asymptomatic hypoglycemia group had lower MG, higher MAGE and CV compared with the other two groups(all P<0.05). Multivariate logistic regression analysis showed that urinary albumin/creatinine ratio (UACR), MAGE, and CV were the risk factors for asymptomatic hypoglycemia, while MG was the protective factor. After adjustment for other risk factors, MAGE was still associated with asymptomatic hypoglycemia ( OR=1.111, 95% CI 0.999-1.235, P=0.049). The sensitivity and specificity of MAGE in predicting asymptomatic hypoglycemia were 0.769 and 0.776, respectively. Conclusions:Patients with asymptomatic hypoglycemia present with larger TIR and MAGE. MAGE, UACR, and CV were risk factors for asymptomatic hypoglycemia. Moreover, MAGE has some predictive value for the occurrence of asymptomatic hypoglycemia.
8.Reoperation for biliary-enteric strictures after hepaticojejunostomy in children with congenital biliary dilatation
Dongyang WU ; Yajun CHEN ; Tingchong ZHANG ; Dayong WANG ; Zengmeng WANG ; Jihang SUN ; Chunhui PENG ; Wenbo PANG ; Kai WANG ; Xinjie HUANG
Chinese Journal of General Surgery 2021;36(9):658-662
Objective:To evaluate clinical characteristics and treatment of postoperative anastomotic stricture in pediatric congenital biliary dilatation patients.Methods:The clinical data of 24 children with postoperative anastomotic stricture from Apr 2012 to Oct 2019 in Beijing Children's Hospital was retrospectively analyzed.Results:There were 6 males and 18 females. Patients were divided into bile- leak group (BL, n=6) and non bile-leak group (NBL, n=18) based on whether there was anastomotic leakage after primary surgery. The main symptoms in BL group was persistent obstructive jaundice, and recurrent cholangitis in NBL group. Postoperative symptoms were first shown in an average of 7.0 months in BL group, compared to 59.0 months in NBL group, P<0.05. In BL group, 4 underwent redoing hepaticojejunostomy, 2 underwent anastomosis plasty. In NBL group, 3 underwent redoing hepaticojejunostomy, 15 did anastomosis plasty with multiple biliary stones found necessitating extraction. After reoperation, one patient had bile leakage, 2 patients had recurrent cholangitis within one-month, 21 patients had uneventful recovery. Five were found to have biliary stones in long-term follow-up. Conclusions:Biliary-enteric anastomotic leakage can cause stricture in postoperative patients of congenital biliary dilatation ,reoperation is necessary in symptomatic patients.
9.A Real-world Study on the Assessment of Pathological Characteristics and Targeted Therapeutic Effect of Non-small Cell Lung Cancer Patients with Positive Driving Genes and High PD-L1 Expression.
Hui ZHANG ; Xinjie YANG ; Kun LI ; Jinghui WANG ; Jialin LV ; Xi LI ; Xinyong ZHANG ; Na QIN ; Quan ZHANG ; Yuhua WU ; Li MA ; Fei GAI ; Ying HU ; Shucai ZHANG
Chinese Journal of Lung Cancer 2021;24(2):78-87
BACKGROUND:
Targeted therapy for patients with driver genes positive and immunotherapy for patients with driver gene-negative but high programmed death ligand 1 (PD-L1) expression are the standards of first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The treatment options for patients with driver gene positive and high PD-L1 expression are still worth exploring.
METHODS:
The characteristics of 315 patients with NSCLC were identified to analyze the clinicopathological characteristics of patients with driver gene positive and high PD-L1 expression, and the efficacy of targeted therapy.
RESULTS:
Among the 315 patients, the total positive rate of driver genes was 62.2%, and the high PD-L1 expression rate (≥50.0%) was 11.2%. The proportion of patients with driver gene positive and high PD-L1 expression was 10.7%. PD-L1 was highly expressed in patients with epidermal growth factor receptor (EGFR) mutation, KRAS mutation, ALK fusion, BRAF mutation, and MET 14 exon skip mutation, the proportions were 7.8% (11/141), 18.2% (4/22), and 23.1%, (3/13), 50.0% (2/4) and 100.0% (1/1) respectively. EGFR mutation positive with PD-L1 high expression was mainly in patients with stage IV lung adenocarcinoma. KRAS mutation positive with PD-L1 high expression was mainly in patients with a history of smoking. Among them, two patients were followed in detail for targeted therapy, who with ALK fusion-positive and PD-L1 high expression (90.0%), EGFR L858R mutation and PD-L1 high expression (70.0%) respectively. The total OS of the patients was 5 months, 2 months.
CONCLUSIONS
The high PD-L1 expression rate in NSCLC patients with different driver gene mutations was variable, which maybe correlated with distinct clinicopathological characteristics. Patients with sensitive mutations and high PD-L1 expression may be less benefit from targeted therapy and have poor prognosis.
10.Establishment of HPLC Fingerprints and Content Determination of 7 Components of Jingu Tongxiao Pill
Shi SUN ; Yifang WANG ; Xinjie ZHAO ; Zhao WANG ; Li ZHANG ; Dandan WANG ; Ailing WU ; Xiaolong WU
China Pharmacy 2021;32(10):1235-1240
OBJECTIVE:To establish the fingerprint of Jingu tongxiao pill ,and to determine the contents of 7 components. METHODS:HPLC method was adopted. The determination was performed on Cosmosil 5C18-MS-Ⅱ column with acetonitrile- 0.02% phosphoric acid solution as mobile phase (gradient elution )at the flow rate of 1.0 mL/min. The detection wavelength was 230 nm and the column temperature was set at 25 ℃. The sample size was 10 μL. HPLC fingerprint of 10 batches of Jingu tongxiao pill was established by using Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition),and common peak was identified by comparing with the mixed reference substance. The contents of corresponding components of the identified common peak were determined by the same HPLC method. RESULTS :There were 20 common peaks in HPLC fingerprint of 10 batches of samples ,and the similarity with the control fingerprint was not less than 0.980. By comparing with the mixed reference substance, 7 components were identified , which were loganic acid ,gentiopicroside,paeoniflorin,salvianolic acid B , cryptotanshinone,tanshinone Ⅰ and tanshinone Ⅱ A. The linear range of the above 7 components were 4.509-45.090, 15.090-150.900,14.985-149.850,14.982-149.820,2.967-29.670,1.944-19.440,3.094-30.940 μg/mL(all r>0.999),respectively. The limits of detection were 0.060 1,0.161 0,0.399 6,0.159 8,0.031 6,0.051 8,0.082 5 μg/mL,respectively. The limits of quantitation were 0.200 4,0.503 0,0.999 0,0.399 5,0.079 1,0.259 2,0.412 6 μg/mL,respectively. RSDs of precision ,stability (24 h) and reproducibility tests were all lower than 3.0% (n=6). Average recoveries were 98.81% -100.28% ,RSDs were 0.20%-1.21%(n=6). In 10 batches of samples ,the contents of the above 7 components were 0.441 0-0.969 4,3.283 4-4.733 4, 1.947 7-3.674 9,1.336 6-2.270 9,0.293 2-0.372 1,0.190 2-0.293 9 and 0.352 8-0.518 8 mg/g,respectively. CONCLUSIONS :In this study,HPLC fingerprint and content determination method of Jingu tongxiao pill are successfully established and can be used for quality control.

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