1.Progress of gene-mediated precision immunotherapy in the treatment of acute myeloid leukemia
Pengbo ZHAO ; Ying ZHU ; Lifang YIN ; Xiaofei XIN
Journal of China Pharmaceutical University 2024;55(1):53-62
		                        		
		                        			
		                        			Acute myeloid leukemia (AML) is a disease caused by abnormal cloning of hematopoietic stem cells in the bone marrow, which leads to accumulation of a large number of abnormally differentiated myeloid cells. It is difficult to cure by traditional treatment. The successful application of chimeric antigen receptor T cell (CAR-T) immunotherapy indicates that the treatment of hematological tumors has entered a new stage of precision immunotherapy. However, CAR-T immunotherapy has been found to have many problems in clinical applications, including long treatment cycle, expensive prices, off-target effects, cytokine release syndrome, etc. Therefore, it is necessary to expand the application of CAR or adopt improved measures to enhance the therapeutic effect. This article reviews the new strategies for genetic engineering modification of CAR immune cells and the research progress and application of in situ programming to generate CAR-T, and besides, briefly introduces the new methods about the delivery of gene drugs in vivo, aiming to provide new ideas and theoretical basis for expanding and improving the application of precision immunotherapy in AML.
		                        		
		                        		
		                        		
		                        	
2.Efficacy of different administration methods for labor analgesia
Huihui LI ; Lifang ZHAO ; Jiefang FAN
Chinese Journal of Primary Medicine and Pharmacy 2024;31(2):239-242
		                        		
		                        			
		                        			Objective:To investigate the clinical efficacy of different administration methods for labor analgesia.Methods:This randomized controlled study was conducted on 152 parturient women who underwent vaginal delivery at the Xinxiang Central Hospital from February to June 2023. These women were divided into a control group and an observation group, with 76 women per group. Women in the control group received 3 mL of 0.1% ropivacaine hydrochloride after routine epidural catheterization, followed by 3 mL of analgesic drugs after 3 minutes. For those without any special reactions, an analgesic pump containing 9 mL of medication was used after 3 minutes until the end of labor. In the observation group, 3 mL of 0.1% ropivacaine hydrochloride was administered as a trial dose before the epidural catheter was inserted into the epidural space. After 3 minutes, the postpartum woman lay flat and was given another 3 mL of analgesic pump medication. After 3 additional minutes, an additional 9 mL of the medication was administered. The analgesic pump was connected and turned on until the catheter was removed after delivery. The epidural catheter failure rate was assessed in each group. Before epidural puncture (T 1), within 30 minutes after the onset of anesthesia (T 2), and at the time of full dilation of the cervix (T 3), Visual Analogue Scale scores, the number of patient attempts to additionally use an analgesia pump, maternal satisfaction, the number of cases requiring cesarean section conversion, the incidence of adverse reactions (such as nausea, vomiting, and fever), and Apgar scores for newborns were recorded in each group. Results:The epidural catheter failure rate in the observation group was 1.3% (1/76), which was significantly lower than 10.5% (8/76) in the control group ( χ2 = 5.79, P < 0.05). At T 2 and T 3, the Visual Analogue Scale score in the observation group was (0.89 ± 0.08) points and (2.1 ± 0.07) points, respectively, which were significantly lower than (2.55 ± 0.07) points and (3.35 ± 0.07) points in the control group ( t = 238.54, 133.17, both P < 0.001). The number of patient attempts to additionally use an analgesia pump in the observation group was (1.00 ± 0.84) counts, which was significantly less than (4.00 ± 0.65) counts in the control group ( t = 29.47, P < 0.001). Maternal satisfaction in the observation group was 100% (76/76), which was significantly higher than 92.1% (70/76) in the control group ( χ2 = 6.25, P < 0.05). The number of cases requiring cesarean section conversion in the observation group was 0 (0/76), which was significantly lower than 52.6% (4/76) in the control group ( χ2 = 4.10, P < 0.05). Conclusion:Administering a trial dose (3 mL) of 0.1% ropivacaine hydrochloride before placing the epidural catheter during labor analgesia can greatly increase the placement success rate of the catheter and enhance pain relief effectiveness. This has a certain clinical application value.
		                        		
		                        		
		                        		
		                        	
3.Effect of different intervention plans on the expression of adhesion related cytokines and clinical outcomes after uterine adhesions separation surgery
Fen ZHAO ; Huanxin ZHONG ; Lifang YOU ; Yi LU ; Hongyin CUI
Chinese Journal of Endocrine Surgery 2024;18(5):739-743
		                        		
		                        			
		                        			Objective:To observe the effects of different intervention schemes on the expression of adhesion-related cytokines, menstrual recovery and clinical outcome of patients after transcervical resection of adhesion (TCRA) .Methods:180 patients received TCRA in our hospital from Feb. 2022 to Feb. 2023 were divided into group A, group B and group C according to different post-operative intervention programs, with 60 patients in each group. Patients in group A were treated with artificial cycle of estrogen and progesterone after surgery. On this basis, patients in group B were placed with a uterine birth control ring, and patients in group C were injected with sodium hyaluronate gel into the uterine cavity. The grade of uterine cavity adhesion, improvement rate of menstruation and pregnancy outcome at 2 months after operation and pregnancy outcome within 1 year after surgery were compared between the three groups at 2 months after operation. The relative mRNA expression of endometrial tissue transforming growth factor β1 (TGF-β1), platelet-derived growth factor BB (PDGF-BB), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and basic fibroblast growth factor (bFGF) at uterine cavity adhesion in each group were detected and compared.Results:At 2 months after surgery, the uterine adhesion rates in group A, group B, and group C were 43.33%, 15.00%, and 11.67%, respectively. There was no significant difference in the uterine adhesion rates between group B and group C ( P>0.05), but they were significantly lower than those in group A ( P<0.05) ; Meanwhile, the degree of intrauterine adhesions in group B and group C was significantly milder than that in group A ( P<0.05). The menstrual improvement rates of group A, group B, and group C at 2 months after surgery were 76.67%, 93.33%, and 96.67%, respectively. There was no significant difference between group B and group C ( P>0.05), but they were all significantly higher than group A ( P<0.05). At 2 months post surgery, the relative expression levels of TGF-β1, PDGF-BB, TIMP-1, and bFGF mRNA in the endometrial tissue at the site of uterine adhesions in group A were 0.77±0.26, 0.58±0.27, 0.54±0.15, and 0.62±0.14, respectively. In group B, they were 0.37±0.16, 0.37±0.14, 0.26±0.11, and 0.29±0.10, respectively. In group C, they were 0.32±0.16, 0.21±0.09, 0.27±0.08, and 0.34±0.18, respectively. The relative expression levels of cytokines in each group were significantly lower than during surgery ( P<0.05). There was no significant difference in the relative expression levels of various cytokines mRNA between group B and group C at 2 months after surgery ( P>0.05), but both were significantly lower than group A ( P<0.05). The pregnancy success rates within 1 year after surgery in group A, group B, and group C were 40.00%, 55.00%, and 58.33%, respectively. The pregnancy success rate in group C was significantly higher than that in group A ( P<0.05) . Conclusions:The application of metauterine contraceptive ring or sodium hyaluronate gel on the basis of estrogen and progesterone treatment after TCRA can effectively prevent postoperative re-adhesion of patients with intrauterine adhesions, improve clinical symptoms, and reduce the expression level of adhesion cytokines. The effects of the two schemes are equivalent.
		                        		
		                        		
		                        		
		                        	
4.Association between short-term exposure to atmospheric fine particulate matter and ozone and inflammatory indicators in peripheral blood of patients with pneumonia
Lulu SONG ; Qi YU ; Nannan LIU ; Yuhui GAO ; Zeyu NIU ; Yan ZHANG ; Huiqiu ZHENG ; Jiayu TIAN ; Junxia LIU ; Lifang ZHAO ; Zhihong ZHANG
Shanghai Journal of Preventive Medicine 2024;36(6):551-558
		                        		
		                        			
		                        			ObjectiveTo explore the association between short-term exposure to atmospheric fine particulate matter (PM2.5) and ozone (O3) and systemic inflammatory indicators in patients with pneumonia, and to identify the susceptible populations. MethodsFrom September 2018 to April 2020, data of 1 480 patients admitted for pneumonia was collected from a tertiary hospital in Taiyuan City. Generalized additive models (GAMs) were used to explore the associations between PM2.5 and O3 exposure and inflammatory indicators of patients with pneumonia; and to explore the susceptibility factors and susceptible populations to PM2.5 and O3 exposures through stratified analyses. ResultsThe short-term exposure to PM2.5 was associated with changes in peripheral blood C-reation protein (CRP), erythrocyte sedimentation (ESR), easinophil (EOS), neutrophil (NEU) and neutrophil-lymphocyte ratio (NLR) in patients with pneumonia, and there were different degrees of hysteresis effects, with the effect values reaching a maximum at lag03, lag03, lag0, lag03, lag03, respectively, which were 4.13% (95%CI: 0.43%‒7.84%), 3.10% (95%CI: 0.24%‒5.97%), 5.27% (95%CI: 3.12%‒7.42%), 1.85% (95%CI: 0.36%‒3.34%), and 2.53% (95%CI: 0.53%‒4.74%) for every 10 μg·m-3 of PM2.5. The changes in O3 concentration were associated with the elevation of peripheral blood PCT and ESR in patients with pneumonia, and their effect values all reached the maximum at lag01 d, every 1 μg·m-3 of O3 elevation increased by 0.38% (95%CI: 0.04%‒0.73%) and 0.47% (95%CI: 0.19%‒0.76%), respectively. Stratified analyses showed that the associations of PM2.5 with peripheral blood CRP, ESR, NEU, and NLR in pneumonia patients were more significant in males, the elderly, and those with onset in the cold season; the associations of O3 with peripheral blood PCT and ESR in pneumonia patients were more significant in the elderly and those with onset in the warm season, and the peripheral blood CRP and PCT in female patients with pneumonia were more susceptible to the changes of O3. ConclusionShort-term exposure to atmospheric PM2.5 and O3 are positively associated with changes in inflammatory indicators in patients with pneumonia, and the effects of PM2.5 on patients with pneumonia are more extensive than those of O3, with a longer lag effect. In addition, elderly patients with pneumonia are more sensitive to air pollution, male patients with pneumonia are more sensitive to PM2.5, and female patients with pneumonia are more sensitive to O3. Cold and warm seasons can exacerbate the effects of PM2.5 and O3 on inflammatory indicators in patients with pneumonia, respectively, and the patients must be protected well. 
		                        		
		                        		
		                        		
		                        	
5.Methodological investigation on bacterial endotoxin in betahistine hydrochloride injection
HAO Gang ; ZHANG Lifang ; WU Xing ; YAN Hao ; ZHAO Yating ; HAN Feng
Drug Standards of China 2024;25(1):082-089
		                        		
		                        			
		                        			Objective: Investigation on the quality control method of bacterial endotoxin in betahistine hydrochloride injection. 
Methods: The method of bacterial endotoxin gel test of 23 batches of betahistine hydrochloride injection from 5 manufacturers was studied. 
Results: The limit value of endotoxin in this product was 3 EU·mg-1, which was suitable for the bacterial endotoxin test of China Pharmacopoeia 2020. 
Conclusion: The quality of betahistine hydrochloride injection can be controlled by bacterial endotoxin test, and the limit of bacterial endotoxin can be set as follows: the content of endotoxin in every 1mg of betahistine hydrochloride should not exceed 3 EU.
		                        		
		                        		
		                        		
		                        	
6.Complete genome sequence and molecular characterization of a human respiratory syncytial virus subtype B strain isolated in Qinghai province
Lifang HE ; Mengqi YIN ; Shengcang ZHAO ; Zhijian TANG ; Youju LEI ; Jinying QI ; Deng TIAN ; Chunxiang WANG
Chinese Journal of Experimental and Clinical Virology 2024;38(5):533-538
		                        		
		                        			
		                        			Objective:To analyze the genetic characteristics of the complete genome of a strain of human respiratory syncytial virus (HRSV) in Qinghai province in 2024.Methods:A total of 300 samples were collected during 2024 influenza surveillance in Qinghai province sentinel hospitals from patients with fever accompanied by severe respiratory infection symptoms. We used real-time fluorescent quantitative reverse transcription polymerase chain reaction RT-PCR) method to screen out HRSV subtype B (HRSVB) positive specimens, whole genome sequencing was performed on positivespecimens meeting the requirements for the sequencing. After downloading the global representative HRSVB genotypes at GenBank database, sequence alignment was performed, related evolutionary tree was built and the calculation and analyses of genetic distance were done, analyses of HRSVB sequencing of sequence homology of nucleotides, amino acids and amino acid mutation were performed.Results:The first strain in Qinghai, China/qinghai/2024-03 had a complete sequence of 15 140 bp nucleotides, with HRSV′s all structural characteristics, and subtype HRSVA prototype strain Long strains of nucleotide the lowest homology was 80.0%, and subtype HRSVB prototype strain nucleotide homology was above 94.7%. The result indicated that the first strain in Qinghai belonged to HRSVB subtype. Genetic evolution shows China/qinghai/2024-03 and USA/WA-S23450/2021 (OR326803.1) and Germany/2021 (OR795235.1) all belong to a branch, they have the closest relationship. Phylogenetic analysis of G gene showed that the strain belonged to BA9 genotype of HRSVB subtype, and the hypervariable regions of the genome were SH and G genes.Conclusions:In this study, the complete genome sequence of HRSV China/qinghai/2024-03 was obtained for the first time, and the basic molecular structural characteristics were elucidated, which filled the gaps in the gene and amino acid data of HRSV in our province, and also provided a basis for HRSV epidemiology.
		                        		
		                        		
		                        		
		                        	
7.Gastrodin improves renal hypertension in rats possibly by inhibiting autophagy signals
Lifang SI ; Tianzhi ZHAO ; Yumin SONG ; Mengyun LI ; Xiang LI ; Feiyao WANG
Chinese Journal of Pharmacology and Toxicology 2024;38(5):369-374
		                        		
		                        			
		                        			OBJECTIVE To explore the mechanism by which gastrodin improves renal hyperten-sion in rats.METHODS A rat model of renal hypertension was established by ligating the renal artery.seventy-five rats were randomly divided into 5 groups(n=15):control group(sham operation group),model group,model+ramipril 1 mg·kg-1,model+gastrodin 100 and 200 mg·kg-1.The systolic blood pressure of the tail artery after modeling>18.12 kPa was regarded as the success of modeling.After the model was established,rats in the model+ramipril group were ig given ramipril 1 mg·kg-1 while the model+gastrodin group was ig given gastrodin 100 and 200 mg·kg-1 respectively for 4 weeks.Colori-metric assay kit was used to detect the serum superoxide dismutase(SOD)activity and malondialde-hyde(MDA)content in rats.ELISA was used to detect serum angiotensin-2(Ang-2)and aldosterone(ALD)contents,as well as serum and thoracic aortic tissue interleukin-1β(IL-1β),IL-6 and tumor necrosis factor α(TNF-α)content.HE staining was performed to detect pathological changes in thoracic aorta tissue of rats.The expressions of autophagy protein miceotubule associated protein light chain 3(LC3)-Ⅱand LC3-Ⅰwere detected by Western blotting.RESULTS The systolic pressure of the tail artery of rats after modeling exceeded 18.12 kPa,indicating that the modeling was successful.Compared with the control group,the contens of Ang-2(P<0.01)and ALD(P<0.01)in the model group were significantly increased,the activity of SOD(P<0.01)in serum and thoracic aorta tissue was significantly decreased,the content of MDA(P<0.01)was significantly increased,the contents of IL-1β,IL-6 and TNF-α in serum and thoracic aorta tissue were significantly decreased(P<0.01)and the ratio of LC-32/LC-31 in thoracic aorta tissue was significantly increased(P<0.01).Compared with the model group,gastrodin significantly increased the systolic pressure of the tail artery(P<0.01),the contents of Ang-2(P<0.01)and ALD(P<0.01)and the activity of SOD(P<0.01)in serum,as well as decreased the contents of MDA,IL-1β,IL-6 and TNF-α(P<0.01)in serum and thoracic aorta tissue.Meanwhile,gastrodin signifi-cantly decreased the ratio of LC3-Ⅱ/LC3-Ⅰ in rat thoracic aorta(P<0.01).CONCLUSION Gastrodin can improve the blood pressure of renal hypertensive rats,and the mechanism is possibly related to the reduction of autophagy protein LC3-Ⅱ/LC3-Ⅰratio.
		                        		
		                        		
		                        		
		                        	
8.Data-Driven Inversion of Hemodynamic Parameters for Combined Stenotic Left Coronary Artery Aneurysms
Zhengjia SHI ; Lifang SUN ; Mingxuan ZHAO ; Mengqiang JI ; Yulong SHI ; Jianbing SANG
Journal of Medical Biomechanics 2024;39(5):853-859
		                        		
		                        			
		                        			Objective To investigate the application of machine learning to predict the hemodynamic parameters of combined stenotic left coronary artery(LCA)aneurysms.Methods Parameterized modeling and simulation based on the geometric parameter range of combined stenosis LCA aneurysms in clinical statistics were conducted.The obtained simulation data was used as the dataset,and two common machine learning models were constructed and trained for optimization to predict two key hemodynamic parameters:wall shear stress(WSS)and pressure.By comparing and analyzing the performances of these models on the training and testing sets,the accuracy of each model was evaluated,and the effectiveness of the data-driven prediction of hemodynamic parameters for LCA aneurysms with concomitant stenosis was verified.Results The effectiveness of machine learning method in inverting the hemodynamic parameters of aneurysms was determined.For WSS prediction,the trained deep learning model and random forest model achieved mean squared error(MSE),mean absolute error(MAE),and determination coefficient R2 of 0.052 8,0.032 2,0.988 3,and 0.078 2,0.046 3,and 0.976 6,respectively.For pressure prediction,the accuracies of the deep learning models and random forest models were comparable,with MSE,MAE,and R2 of 4.67×10-6,3×10-4,0.999 7,and 1.07×10-5,5×10-4,and 0.999 3,respectively.Conclusions Machine learning methods show high accuracy in predicting the hemodynamic parameters of combined stenotic coronary artery aneurysm models.The predictive accuracy of the model,computational efficiency,and needs of the application scenarios need to be considered in machine learning prediction so that the appropriate model can be selected according to the specific situation.This study has clinical significance,helping doctors to more accurately evaluate a patient's condition and provide new ideas and method for the diagnosis and treatment of cardiovascular diseases.
		                        		
		                        		
		                        		
		                        	
9.Chaihu Shugansan and Its Modified Formulas in Treatment of Functional Dyspepsia: A Review
Wei ZHAO ; Yaxi ZHANG ; Yuxuan JIANG ; Jiaqing DAI ; Lifang GUO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):248-255
		                        		
		                        			
		                        			Chaihu Shugansan composed of Bupleuri Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, Aurantii Fructus, Citri Reticulatae Pericarpium, Cyperi Rhizoma, and Glycyrrhizae Radix et Rhizoma has the effects of soothing liver, relieving depression, regulating Qi movement, and relieving pain. It is a classic formula for treating gastric distension recommended by doctors of later ages. This article systematically reviews the clinical application and basic experimental progress of Chaihu Shugansan in the treatment of functional dyspepsia. In modern clinical practice, Chaihu Shugansan and its modified formulas are used to treat functional dyspepsia, and they can be applied in combination with other formulas (Si Junzitang, Jinlingzisan, Zhizhuwan, etc.), western medicine (domperidone tablets, deanxit, Saccharomyces boulardii, etc.), traditional Chinese medicine (TCM) acupuncture and other therapies. The results of clinical studies have shown that Chaihu Shugansan and its modified formulas can significantly reduce the Hamilton depression scale (HAMD) score, Hamilton anxiety scale (HAMA) score, and TCM syndrome score, ameliorate the symptoms, improve the quality of life, and decrease the recurrence rate. The experimental pharmacological studies have demonstrated that Chaihu Shugansan can inhibit the autophagy of Cajal interstitial cells, regulate the endoplasmic reticulum stress signaling pathway, and modulate the brain-gut peptide level to improve the gastrointestinal motility. Chaihu Shugansan can inhibit the expression of 5-hydroxytryptamine in the colon tissue and reduce the abdominal withdrawal reflex (AWR) score to improve visceral hypersensitivity. Furthermore, Chaihu Shugansan can lower the levels of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α to repair duodenal mucosal inflammation. In addition, it can regulate intestinal flora to maintain intestinal flora balance. The main active ingredients such as saikosaponin, paeoniflorin, hesperidin, and naringin in Chaihu Shugansan can exert anti-inflammatory, antioxidant, and antimicrobial effects. 
		                        		
		                        		
		                        		
		                        	
10.Effect of early liraglutide administration on cardiometabolic risk factors in T2DM patients with coronary microvascular disease
Hongxu ZHANG ; Tong CHEN ; Lifang ZHANG ; Fanqi GENG ; Zhao LI ; Xuejuan ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(8):892-897
		                        		
		                        			
		                        			Objective To investigate the effect of early combined use of liraglutide on cardiometa-bolic risk factors and prognosis in patients with T2DM and CMVD.Methods A total of 124 T2DM patients with concomitant CMVD admitted in our hospital from May 2021 to June 2023 were enrolled,and divided into the liraglutide group(n=59)and the non-liraglutide group(n=65)according to taking liraglutide or not.The main observation indicators were compared between the two groups,including cardiometabolic risk factors,such as Hcy,UA,FPG,eGFR,HbA1c,hs-CRP,WC,BMI,WWI,and echocardiographic indicators,such as LAD,LVEDD,LVPWT,IVST,E/e',e',LVEF,LAVI,LVMI,and RWT.And the incidence of adverse reactions and read-mission rates were recorded during follow-up.Results After treatment,in the liraglutide group,Hcy,UA,FPG,HbA1c,hs-CRP,WC,BMI,WWI,E/e',LAVI,LVMI,RWT,IVST and LVPWT values,and anteroposterior,transverse and long diameters of left atrium were all lower than before treatment,and eGFR and e'value were increased(P<0.05,P<0.01),and no significant difference was seen in LVEF and LVEDD(P>0.05).The non-liraglutide group obtained lower HbA1c,FPG,BMI,E/e'and LAVI values,and transverse diameter of left atrium,elevated LVPWT and e'value(P<0.05,P<0.01),and no obvious changes in Hcy,UA,eGFR,hs-CRP,WC,WWI,BMI,LVEF,LVMI,RWT,LVEDD,IVST,and anteroposterior and long diameters of left atrium when compared with the indicators before treatment(P>0.05).At the end of the fol-low-up,when compared with the non-liraglutide group,the liraglutide group had more significant decreases in E/e',LAVI,LVMI and RWT values and increase in e'value(P<0.05,P<0.01),and higher total effective rates(94.92%vs 72.31%,P<0.01).What's more,the readmission rate due to adverse cardiovascular events was notably lower in the liraglutide group and the non-liraglutide group(3.39%vs 15.38%,P<0.05).Conclusion Compared with BMI,WWI may be more sensi-tive in reflecting changes in cardiometabolic risk factors in T2DM patients with CMVD;Early combined application of liraglutide has good efficacy and safety,and exerts multiple cardiovascular protective effects,including reducing cardiometabolic risk factors,improving cardiac diastolic function and renal function,inhibiting chronic inflammation and decreasing the occurrence of ad-verse cardiovascular events in the patients.
		                        		
		                        		
		                        		
		                        	
            
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