1.Effect of Pyridoxamine and Telmisartan on the Indexes of Myocardial Remodeling in Spontaneous Hypertensive Rats
Weiping ZHENG ; Pengli ZHU ; Feng LI ; Huizhen YU ; Fan LIN ; Hong LIN ; Kaiyang LIN
Chinese Circulation Journal 2015;(7):689-693
Objective: To observe the effect of pyridoxamine and telmisartan on the indexes of myocardial remodeling in spontaneous hypertensive rats (SHR). Methods: A total of 48 male SHR at 22 weeks of age were randomly divided into 4 groups:①Hypertension (H) control group, the rats received distilled water 2 ml/d,②telmisartan (T) group, the rats received telmisartan 6 mg/(kg.d),③pyridoxamine (P) group, the rats received pyridoxamine 200 mg/(kg.d),④Combination (TP) group, the rats received both telmisartan and pyridoxamine. All animals were treated for 16 weeks and the systolic blood pressure (SBP) was measured before and after treatment. After treatment, the serum levels of nitric oxide (NO) and super oxide dismutase (SOD) were examined by chemiluminescent method, advanced glycation end-products (AGEs) was detected by ELISA, left ventricular weight index and collagen volume fraction (CVF) in myocardial tissue were calculated, the mRNA expression of myocardial receptor of advanced glycation end products (RAGE) was evaluated by real time RT-PCR. Results: Compared with H group, SBP levels were decreased in T and TP groups,P<0.01, while SBP in P group stayed similar,P>0.05. Compared with H group, the serum levels of NO and SOD were increased in T, P and TP groups,P<0.01; while compared with T group and P group, the levels of NO and SOD were further increased in TP group,P<0.05. Compared with H group, left ventricular weight index and CVF were decreased in T, P and TP groups,P<0.01; while compared with T group and P group, left ventricular weight index and CVF were further decreased in TP group,P<0.05. Pyridoxamine and telmisartan had the coordinative effect on left ventricular weight index and CVF, P<0.05. The serum levels of AGEs were lower in T group (5.99 ± 0.51) mg/L, P group (5.57 ± 0.91) mg/L and TP group (5.24 ± 0.63) mg/L than that in H group, (6.71 ± 0.50) mg/L,P<0.01; while compared with T group and P group, AGEs was further decreased in TP group,P<0.05. The mRNA expressions of RAGE were reduced in T group (0.035 ± 0.010), P group (0.036 ± 0.005) and TP group (0.024 ± 0.007) than that in H group (0.053 ± 0.010),P <0.01; while compared with T group and P group, the mRNA of RAGE was further reduced in TP group, P<0.05. Conclusion: Pyridoxamine could improve the oxidative stress and the indexes of myocardial remodeling independently from decreasing blood pressure in SHR. Combined intervention of P and T may break the coordination systems between AGEs-RAGE and renin-angiotensin, therefore further improve the indexes of myocardial remodeling in SHR.
2.Effects of Jianpi Yichang Powder on Expressions of IL-1β and IL-18 of NLRP3 Signaling Pathway in Ulcerative Colitis Rats
Xiaoyuan LIN ; Kaiyang LI ; Jie GUAN ; Jiemin LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):117-121
Objective To explore the effects of Jianpi Yichang Powder on the expressions of interleukin(IL)-1β and IL-18 of NLRP3 signaling pathway in ulcerative colitis(UC)model rats.Methods Ten rats were randomly selected from 40 SD rats as the normal group,and the other rats freely drank 5%dextran sulfate solution for 7 days to replicate UC rats model.The model rats were randomly divided into model group,sulfasalazine group and Jianpi Yichang Powder group,with 10 rats in each group.Jianpi Yichang Powder group and sulfasalazine group were given corresponding liquid medicine for gavage,and the normal and model groups were given equivalent volume distilled water for gavage for consecutive 14 d.The general status was observed,and the disease activity index(DAI)was scored,the contents of NLRP3,apoptosis-associated spotted proteins(ASC),and Caspase-1 in serum were detected by ELISA,the expressions of IL-1β and IL-18 protein and mRNA in colon tissue were detected by immunohistochemistry,Western blot and RT-PCR respectively.Results Compared with the normal group,the general status of the rats in model group was relatively worse,and DAI score significantly increased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum were significantly increased(P<0.01),the expressions of IL-1β and IL-18 protein and mRNA in colon tissue were significantly increased(P<0.01).Compared with the model group,the general status of the rats in Jianpi Yichang Powder group and sulfasalazine group were significantly improved,DAI score significantly decreased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum significantly reduced(P<0.05,P<0.01),and the expressions of IL-1β and IL-18 protein and mRNA in colon tissue significantly decreased(P<0.05,P<0.01).Conclusion Jianpi Yichang Powder can inhibit IL-1β and IL-18 expression of NLRP3 signaling pathway to reduce colon immune inflammatory damage,thus play a role in treating UC.
3.Application value of regional oxygen saturation in prognosis evaluation of patients with acute lower limb ischemia
Kaiyang WANG ; Ting WANG ; Lin XU ; Rennan GUO
Chinese Journal of Emergency Medicine 2024;33(3):371-376
Objective:To explore the application value of regional oxygen saturation (rSO 2) level in the prognosis evaluation of patients with acute lower limb ischemia (ALLI). Methods:Retrospective analysis of clinical data of 82 ALLI patients admitted to the ICU of Xinjiang Uygur Autonomous Region People's Hospital from June 2021 to June 2022. The subjects were divided into event group and non-event group according to the incidence of adverse events during the follow-up. The general clinical data of the two groups were compared. Multiple stepwise linear regression was used to analyze the independent related factors of rSO 2. Multivariate Cox regression was used to analyze independent risk factors of adverse events. Receiver operating characteristic (ROC) curve was used to obtain the optimal cut-off value of rSO 2 prediction adverse events. The subjects were divided into high-value group and low-value group according to the optimal cut-off value. Kaplan-Meier curve was used to analyze the difference in survival rate between groups during the follow-up. Results:A total of 82 ALLI patients were included in this study, and the incidence of adverse events during follow-up was 25.6% (21 cases). The rSO 2 of four periods and maximum, minimum, average and ankle-brachial index in the event group were significantly lower than those in the non-event group. The troponin I, troponin T, myoglobin, creatine kinase, C-reactive protein, and lactate in the event group were significantly higher than those in the non event group ( P?0.05). Multiple stepwise linear regression analysis showed that: C-reactive protein ( β=-0.320, P=0.002), lactate ( β=-0.262, P=0.009), troponin Ⅰ ( β=-0.230, P=0.025), and smoking history ( β=-0.211, P=0.034) were all independent predictors of rSO 2. Multivariate Cox regression analysis showed that 24 h rSO 2 (mean) was an independent influencing factor for adverse events in ALLI patients (adjusted HR=0.67, 95% CI:0.54-0.83, P<0.001). The 24 h rSO 2 (mean) was good in predicting the incidence of adverse events at 30, 60, and 90 days in ALLI patients (AUC were 0.934, 0.867 and 0.823), and the corresponding optimal cut-off values of rSO 2 were 59.36, 59.03 and 59.03. The sensitivity and specificity to predict adverse events in ALLI patients were 85.7% and 85.3% when the 24 h rSO 2 (mean) was 59.36 as the best cut-off value. According to the optimal cut-off , the subjects were divided into high value group (rSO 2>59.36%, 59 cases) and low value group (rSO 2≤59.36%, 23 cases), Kaplan Meier survival curve analysis showed that there was significant difference in event free survival between the two groups ( P<0.001), the high value group significantly better than the low value group. Conclusion:The 24 h rSO 2 (mean) is an independent influencing factor for adverse events in ALLI patients, and has good predictive value for prognosis.
4.Research Progress in the Treatment of Ulcerative Colitis with Sishen Pills
Kaiyang LI ; Mei YANG ; Qi ZHAO ; Jing HUANG ; Xiaoyuan LIN ; Jiemin LIU ; Zhenfan GUO ; Hui SHI ; Yueyue YANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):180-185
Sishen Pills is a classic prescription for the treatment of spleen and kidney diarrhea,which has the effect of warming the kidney and the spleen,astringent intestine and antidiarrheal.In modern clinical application,the modified prescriptions based on Sishen Pills,combined with other treatments of TCM and integrated traditional Chinese and Western medicine are often used to treat ulcerative colitis with spleen-kidney yang deficiency syndrome,and the curative effect is remarkable.Experimental pharmacological studies have shown that Sishen Pills may achieve the purpose of ulcerative colitis by regulating the expression of related signaling pathway proteins,regulating inflammatory factors,inhibiting inflammatory response,regulating autophagy,regulating intestinal flora,improving intestinal mucosal permeability,repairing intestinal mucosal barrier,regulating cellular energy metabolism,anti-oxidative stress,regulating cellular immune function,etc.In this article,the research status of Sishen Pills in the treatment of ulcerative colitis was sorted out and summarized,in order to provide reference for further study of its mechanism and clinical application.
5.Research Progress in Intervention of Chinese Materia Medica in Th17/Treg Balance in the Treatment of Ulcerative Colitis
Kaiyang LI ; Mei YANG ; Jing HUANG ; Xiaoyuan LIN ; Jiemin LIU ; Yun TANG ; Zhenfan GUO ; Hui SHI ; Yueyue YANG ; Caiyu HUANG ; Qi ZHAO
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(10):191-196,封3
Pathological mechanism of ulcerative colitis(UC)is not fully clear,which may be the result of Th17/Treg immune imbalance and the interaction of multiple complex factors.Numerous studies have found that classical TCM prescriptions,experienced formulas and TCM active components could regulate Th17/Treg balance by intervening in cytokines,transcription factors,and signaling pathways,restore intestinal mucosal immune function,suppress intestinal mucosal inflammatory response,and repair intestinal mucosal barrier damage.Based on the research status of UC,Th17/Treg balance and TCM treatment,this article reviewed the relationship between Th17/Treg balance and UC,and explained the key role of Th17/Treg balance in the occurrence and development of UC.At the same time,the Chinese materia medica targeting to regulate the balance of Th17/Treg in the treatment of UC in recent years was summarized,in order to provide reference for the treatment of UC.
6.Effect of Jianpi Yichang Powder on NLRP3/ASC/Caspase-l Signaling Pathway in Rats with Ulcerative Colitis
Xiaoyuan LIN ; Hang NING ; Kaiyang LI ; Jie GUAN ; Li WANG ; Chunhong LIU ; Jiemin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):154-161
ObjectiveTo explore the effect of Jianpi Yichang power on the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome signaling pathway in a rat model of ulcerative colitis (UC). MethodSixty Sprague-Dawley rats were randomly divided into a normal group (n=10) and an experimental group (n=50). The experimental group received 5% dextran sulfate sodium (DSS) solution freely for 7 days to induce UC, and then they were further randomly divided into model group, sulfasalazine (0.3 g·kg-1) group, and high-, medium-, and low-dose Jianpi Yichang power groups (54.4, 27.2, 13.6 g·kg-1) for continuous treatment of 14 days. The general condition of the rats was observed and recorded daily, and the disease activity index (DAI) was scored before and after treatment. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the serum of rats in each group. Hematoxylin-eosin (HE) staining was performed to observe the histopathological changes in the colon tissue. Immunohistochemistry, Western blot, and Real-time polymerase chain reaction (Real-time PCR) were used to detect the positive protein expression, protein expression, and mRNA expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cysteine aspartate-special proteases-1(Caspase-1) in the colon tissue. ResultCompared with the condition in the normal group, the general condition of rats in the model group was relatively poor, with increased DAI scores (P<0.01), pathological changes in the colon, increased levels of IL-1β and IL-18 in the serum (P<0.01), and enhanced positive protein expression, protein expression, and mRNA expression of NLRP3, ASC, and Caspase-1 in the colon tissue (P<0.01). Compared with the condition in the model group, the general condition of rats in the Jianpi Yichang power groups at various doses improved significantly, with reduced DAI scores (P<0.05, P<0.01), alleviated pathological changes in the colon as revealed by HE staining, and reduced protein expression levels of NLRP3 and Caspase-1 in the colon tissue (P<0.05, P<0.01). The serum levels of IL-1β and IL-18, and ASC protein expression in the colon, as well as the mRNA expression levels of NLRP3, ASC, and Caspase-1, decreased in the high- and medium-dose Jianpi Yichang power groups (P<0.05, P<0.01). The positive protein expression levels of NLRP3, ASC, and Caspase-1 were reduced in the high-dose Jianpi Yichang power group (P<0.01). The positive protein expression levels of ASC and Caspase-1 were reduced in the medium-dose Jianpi Yichang power group (P<0.05). The mRNA expression level of ASC was reduced in the low-dose Jianpi Yichang power group (P<0.05). ConclusionJianpi Yichang power can reduce colon immune inflammatory damage by regulating the NLRP3 inflammasome signaling pathway, thereby exerting a role in treating UC.
7.A trinity strategy for the treatment of multiple orthopedic trauma and assessment of its clinical application
Xiao CHEN ; Guangchao WANG ; Hao ZHANG ; Kaiyang LYV ; Qirong ZHOU ; Yunfei NIU ; Yan HU ; Yuanwei ZHANG ; Zuhao LI ; Hao SHEN ; Jin CUI ; Sicheng WANG ; Zhengrong GU ; Zhen GENG ; Dongliang WANG ; Zhehao FAN ; Shihao SHENG ; Chongru HE ; Jun FEI ; Yunfeng CHEN ; Haodong LIN ; Guohui LIU ; Zhiyong HOU ; Jiacan SU
Chinese Journal of Trauma 2024;40(10):888-896
Objective:To explore the clinical value of a trinity strategy for the treatment of multiple orthopedic trauma.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 267 patients with multiple orthopedic trauma admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Navy Medical University from June 2013 to May 2023, including 862 males and 405 females, aged 18-93 years [(55.2±19.8)years]. Associated injuries included hemorrhagic shock in 632 patients, traumatic wet lung in 274, cranial injuries in 135, abdominal and pelvic bleeding in 116, pneumothorax in 89, urinary injury in 13, and vesical rupture in 8. All the patients were treated with the trinity strategy and the treatment process was divided into the phases of first aid, remodeling, and rehabilitation. The first aid phase focused on stabilizing symptoms and saving lives; the remodeling phase centered on restoring the anatomical structure and alignment; the rehabilitation phase aimed for functional recovery through the integration of both Western and traditional Chinese medicine. The all-cause mortality within 30 days after surgery and fracture healing time were calculated; the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, Hospital for Special Surgery (HSS) knee score and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score at the last follow-up and the overall excellent and good rate of all joint function scores were measured. The short form health survey (SF-36) scores were collected preoperatively and at 6 months postoperatively, including 8 aspects such as physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The incidence of postoperative complications was recorded.Results:All the patients were followed up for 6-18 months [(10.2±4.2)months]. The mortality rate during the acute phase (within 30 days after surgery) was 2.37% with 12 deaths due to hemorrhagic shock, 10 due to traumatic brain injury, 6 due to multiple organ dysfunction syndrome (MODS), and 2 due to pulmonary infection. The average fracture healing time averaged 3.8-18 months [(11.5±4.2)months], with 89.49% of the patients having bone union within 12 months after surgery, 8.93% having bone union within 18 months after surgery, and 1.58% undergoing reoperation. For the patients with internal fixation failure and nonunion, the average healing time was extended to (10.2±2.2)months and (13.7±3.3)months respectively. At the last follow-up, the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, HSS knee score, and AOFAS ankle-hindfoot score were 83.93%, 90.24%, 94.12%, 85.57%, 88.46%, and 92.31% respectively, with an overall excellent and good rate of 89.11%. At 6 months after surgery, the SF-36 scores of all the patients in the eight dimensions,including the physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health were (74.4±8.6)points, (44.7±14.4)points, (77.4±10.9)points, (68.4±18.2)points, (72.5±16.0)points, (76.8±8.7)points, (49.9±17.6)points, and (72.8±17.9)points, significantly improved compared with those before operation [(63.4±12.7)points, (30.9±17.4)points, (56.4±18.0)points, (55.4±24.7)points, (53.5±21.0)points, (55.8±24.3)points, (36.9±24.0)points, (58.8±21.6)points] ( P<0.01). Complications of different degrees occurred in 214 patients (16.89%), including lung infections in 118 patients (9.31%), lower extremity deep vein thrombosis in 50(3.95%), pressure injuries in 26(2.05%), internal fixation failure in 12(0.95%), and nonunion in 8(0.63%). Conclusions:The trinity strategy provides whole-process management, personalized treatment, and overall rehabilitation for multiple orthopedic trauma. It can decrease mortality, shorten fracture healing time, improve joint function and quality of life, and reduce the incidence of complications.
8.Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT)
Huiqiang HUANG ; Zhiming LI ; Lihong LIU ; Liang HUANG ; Jie JIN ; Hongyan TONG ; Hui ZHOU ; Zengjun LI ; Zhenqian HUANG ; Wenbin QIAN ; Kaiyang DING ; Quande LIN ; Ming HOU ; Yunhong HUANG ; Jingbo WANG ; Pengcheng HE ; Xiuhua SUN ; Xiaobo WANG ; Zunmin ZHU ; Yao LIU ; Jinhai REN ; Huijing WU ; Liling ZHANG ; Hao ZHANG ; Liangquan GENG ; Jian GE ; Ou BAI ; Liping SU ; Guangxun GAO ; Xin LI ; Yanli YANG ; Yijian CHEN ; Aichun LIU ; Xin WANG ; Yi WANG ; Liqun ZOU ; Xiaobing HUANG ; Dongping HUANG ; Shujuan WEN ; Donglu ZHAO ; Jun MA
Journal of Leukemia & Lymphoma 2023;32(8):457-464
Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.
9.Clinical features and outcomes of newly diagnosed follicular lymphoma concurrent with diffuse large B-cell lymphoma component
Zhijuan LIN ; Jie ZHA ; Shuhua YI ; Zhifeng LI ; Lingyan PING ; Xiaohua HE ; Haifeng YU ; Zhong ZHENG ; Wei XU ; Feili CHEN ; Ying XIE ; Biyun CHEN ; Huilai ZHANG ; Li WANG ; Kaiyang DING ; Wenyu LI ; Haiyan YANG ; Weili ZHAO ; Lugui QIU ; Zhiming LI ; Yuqin SONG ; Bing XU
Chinese Journal of Hematology 2022;43(6):456-462
Objective:To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component.Methods:1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis.Results:146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) ( P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS ( P=0.006) , while LDH higher than normal was an independent risk factor for OS ( P=0.031) . Conclusion:FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.