1.Mechanism of vanillic acid against cardiac fibrosis induced by isoproterenol in mice based on Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways.
Hai-Bo HE ; Mian WU ; Jie XU ; Qian-Qian XU ; Fang-Zhu WAN ; Hua-Qiao ZHONG ; Ji-Hong ZHANG ; Gang ZHOU ; Hui-Lin QIN ; Hao-Ran LI ; Hai-Ming TANG
China Journal of Chinese Materia Medica 2025;50(8):2193-2208
This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals
;
Isoproterenol/adverse effects*
;
Male
;
Mice
;
Signal Transduction/drug effects*
;
Vanillic Acid/administration & dosage*
;
Dynamins/genetics*
;
Mice, Inbred C57BL
;
Fibrosis/genetics*
;
Apoptosis/drug effects*
;
Mitochondria/metabolism*
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
Myocardium/metabolism*
;
Humans
2.Effect of high ligation of spermatic vein on leukocytes in expressed prostate secretion of patients with chronic prostatitis and varicocele.
Ji-Yang DING ; Peng ZHANG ; Chun-Hua NIU ; Hai-Yong LI ; Wen-Zhu XU ; Ying-Chen ZHANG ; Gang MA
National Journal of Andrology 2025;31(4):319-322
OBJECTIVE:
To investigate the effect of laparoscopic high ligation of spermatic cord vein in patients with chronic prostatitis and varicocele prostatitis.
METHODS:
A total of 90 varicocele patients were selected from January 2016 to December 2020, including 33 patients with chronic prostatitis. Changes of white blood cell count, National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score and serum testosterone level in the expressed prostate secretion (EPS) were observed before and after the operation of laparoscopic high ligation of spermatic vein.
RESULTS:
All patients were followed up three months after the surgery. There was no significant difference in the white blood cell counts in EPS, NIH-CPSI score, and serum testosterone level in patients with varicocele-only who underwent high ligation surgery after the operation. However, the white blood cell count in the EPS of patients with chronic prostatitis was lower than that before 3 months of operation ( [12.39±4.23]×109/L vs [21.36±5.05]×109/L). The NIH-CPSI score was significantly lower than that before operation ( [12.71±6.21] vs [26.76±8.43]). And the serum testosterone level was higher than that before operation ([4.34±1.77]ng/ml vs [2.36±1.05]ng/ml).
CONCLUSION
Laparoscopic high ligation of the spermatic vein in patients with chronic prostatitis and varicocele could effectively reduce the number of white blood cells in the EPS, boost the level of serum testosterone and improves symptoms of chronic prostatitis.
Male
;
Humans
;
Varicocele/surgery*
;
Prostatitis/blood*
;
Ligation
;
Spermatic Cord/blood supply*
;
Testosterone/blood*
;
Chronic Disease
;
Prostate/metabolism*
;
Veins/surgery*
;
Leukocyte Count
;
Leukocytes
;
Laparoscopy
;
Adult
3.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
4.Real-time traking and virtual reality technology-assisted trauma orthopaedic surgery robot for femoral neck fractures
Wei-Gang LOU ; Jian-Ming CHEN ; Shuai-Yi WANG ; Hai-Yang LI ; Ding XU
China Journal of Orthopaedics and Traumatology 2024;37(2):124-128
Objective To investigate the effectiveness of real-time tracking and virtual reality technology(RTVI)used to assist the intraoperative alignment of the trauma orthopaedic surgery robot for the treatment of femoral neck fractures and its impact on the treatment outcome.Methods A retrospective analysis was conducted on 60 patients with femoral neck fractures treated with trauma orthopedic robotic surgery from September 2020 to September 2022.Patients were divided into two groups according to whether RTVI technology was used during surgery to assist robotic surgery.There were 28 patients in the RTVI group(12 males and 16 females),with an average age of(46.2±9.3)years old ranging from 28 to 60 years old.There were 32 patients in the simple Tianji surgical robot group,including 15 males and 17 females,aged(48.2±7.8)years old ranging from 32 to 58.The number of registered fluoroscopy,operation time,total number of intraoperative fluoroscopy,intraoperative blood loss,and hospitalization time of the two groups of patients were observed and recorded.All patients received regular follow-up after surgery,and hip X-rays were routinely reviewed to record Garden alignment index,fracture healing time,postoperative complications,and Harris score.Results All 60 patients were followed up.The RTVI group was followed up for 9 to 16 months with an average of(13.0±l.2)months,and the Tianji surgical robot group alone was followed up for 10 to 14 months with an average of(12.0±1.3)months.During the follow-up period,the femoral neck fractures of both groups of patients healed well,and no complications such as internal fixation loosening and incision infection occurred.The number of registered fluoroscopy,operation time,and number of intraoperative fluoroscopy of patients in the RTVI group were significantly better than those in the simple Tianji surgical robot group(P<0.01).There was no statistically significant difference in intraoperative blood loss,hospital stay,Garden alignment index,fracture healing time,and hip Harris score between two groups(P>0.05).Conclusion Although RTVI technology assisted by the surgical robot for femoral neck fracture surgery has little impact on its postoperative outcome,it can effectively reduce the operating time,the number of intraoperative X-ray projections,and the risk of intraopera-tive radiation exposure to patients.It also shortened the learning curve of the operator and better reflected the precision and ef-ficiency of the trauma orthopaedic surgery robot.
5.Comparative study of two fixation methods in single segment interbody fusion and fixation with unilateral dual channel spinal endoscopic technique.
Ze-Xuan WU ; Tao WANG ; Zhi-Gang LEI ; Xiao-Lin LI ; Hao-Zhe LIU ; Xiao-Yang LI ; Xin-Xin BAI ; Hong-Hai XU
China Journal of Orthopaedics and Traumatology 2024;37(12):1158-1163
OBJECTIVE:
To explore clinical efficacy of unilateral and bilateral nail-rod system fixation in single-level intervertebral fusion fixation of lumbar disc herniation (LDH) and instability with unilateral dual-channel spinal endoscopy.
METHODS:
The clinical data of 63 patients with LDH complicated with instability treated by unilateral double-channel spinal endoscopy from March 2021 to June 2022 were retrospectively analyzed. According to intraoperative fixation methods, the patients were divided into two groups, included unilateral nail rod system fixation group(unilateral group) and bilateral nail rod system fixation group(bilateral group). There were 31 patients in unilateral group, including 15 males and 16 females; aged from 40 to 67 years old with an average of (54.65±7.32) years old; 3 patients with L3,4, 15 patients with L4,5, 13 patients with L5S1. There were 32 patients in bilateral group, including 18 males and 14 females, aged from 43 to 68 years old with an average of (56.19±6.63) years old;4 patients with L3,4, 17 patients with L4,5, 11 patients with L5S1. The time of operation, length of incision, operation time, length of hospital stay, cost of treatment, occurrence of complications and adverse events were recorded and compared between two groups. Visual analogue scale (VAS) of lumbar and leg pain, Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI) were compared before operation, 3 and 12 months after operation. MacNab standard was used to evaluate clinical effect.
RESULTS:
Both of two groups were successfully completed operation and followed up. In unilateral fixation group, follow-up time, operation time, incision length, postoperative ambulation time, hospital stay and treatment cost were (11.81±1.08) months, (122.48±13.86) min, (3.15±0.45) cm, (3.06±0.73) d, (6.87±1.09) d, and (3.49±0.09) ten thousand yuan;while (11.47±1.16) months, (134.94±10.94) min, (6.45±0.83) cm, (3.19±0.86) d, (7.03±1.03) d, (3.77±0.12) ten thousand yuan in bilateral fixation group, respectively;there were significant differences in operation time, incision length and treatment cost between two groups (P<0.05), no significant difference in follow-up time, postoperative ambulation time and hospital stay (P>0.05). There were no significant difference in VAS of low back pain, JOA score, ODI and MacNab grade between two groups before and after operation (P>0.05). No significant complications and adverse events were observed between two groups after operation.
CONCLUSION
Both of unilateral and bilateral nail rod system for the treatment of LDH with instability could achieve the expected results. Unilateral fixation has more advantageous than bilateral fixation in terms of operation time, incision length and treatment cost. For patients with osteoporosis before operation or insufficient fixation strength of unilateral pedicle nails during surgery, bilateral fixation is feasible to enhance reliability of fixation.
Humans
;
Male
;
Female
;
Middle Aged
;
Spinal Fusion/methods*
;
Endoscopy/methods*
;
Aged
;
Adult
;
Intervertebral Disc Displacement/surgery*
;
Lumbar Vertebrae/surgery*
;
Retrospective Studies
6.Long-Term Prognosis of Different Reperfusion Strategies for ST-Segment Elevation Myocardial Infarction in Chinese County-Level Hospitals: Insight from China Acute Myocardial Infarction Registry.
Chao WU ; Qiong Yu ZHANG ; Ling LI ; Xu Xia ZHANG ; Yong Chen CAI ; Jin Gang YANG ; Hai Yan XU ; Yan Yan ZHAO ; Yang WANG ; Wei LI ; Chen JIN ; Xiao Jin GAO ; Yue Jin YANG ; Shu Bin QIAO
Biomedical and Environmental Sciences 2023;36(9):826-836
OBJECTIVE:
To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with different reperfusion strategies in Chinese county-level hospitals.
METHODS:
A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. The success of fibrinolysis was assessed according to indirect measures of vascular recanalization. The primary outcome was 2-year mortality.
RESULTS:
Reperfusion therapy was used in 1,080 patients (42.9%): fibrinolysis ( n= 664, 61.5%) and primary percutaneous coronary intervention (PCI) ( n= 416, 38.5%). The most common reason for missing reperfusion therapy was a prehospital delay > 12 h (43%). Fibrinolysis [14.5%, hazard ratio ( HR): 0.59, 95% confidence interval ( CI) 0.44-0.80] and primary PCI (6.8%, HR= 0.32, 95% CI: 0.22-0.48) were associated with lower 2-year mortality than those with no reperfusion (28.5%). Among fibrinolysis-treated patients, 510 (76.8%) achieved successful clinical reperfusion; only 17.0% of those with failed fibrinolysis underwent rescue PCI. There was no difference in 2-year mortality between successful fibrinolysis and primary PCI (8.8% vs. 6.8%, HR = 1.53, 95% CI: 0.85-2.73). Failed fibrinolysis predicted a similar mortality (33.1%) to no reperfusion (33.1% vs. 28.5%, HR= 1.30, 95% CI: 0.93-1.81).
CONCLUSION
In Chinese county-level hospitals, only approximately 2/5 of patients with STEMI underwent reperfusion therapy, largely due to prehospital delay. Approximately 30% of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years. Quality improvement initiativesare warranted, especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.
Humans
;
ST Elevation Myocardial Infarction/therapy*
;
Percutaneous Coronary Intervention
;
East Asian People
;
Treatment Outcome
;
Myocardial Reperfusion
;
Myocardial Infarction
;
Registries
;
Hospitals
7.To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia.
Xiao Shuai ZHANG ; Bing Cheng LIU ; Xin DU ; Yan Li ZHANG ; Na XU ; Xiao Li LIU ; Wei Ming LI ; Hai LIN ; Rong LIANG ; Chun Yan CHEN ; Jian HUANG ; Yun Fan YANG ; Huan Ling ZHU ; Ling PAN ; Xiao Dong WANG ; Gui Hui LI ; Zhuo Gang LIU ; Yan Qing ZHANG ; Zhen Fang LIU ; Jian Da HU ; Chun Shui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yan Qiu HAN ; Li E LIN ; Zhen Yu ZHAO ; Chuan Qing TU ; Cai Feng ZHENG ; Yan Liang BAI ; Ze Ping ZHOU ; Su Ning CHEN ; Hui Ying QIU ; Li Jie YANG ; Xiu Li SUN ; Hui SUN ; Li ZHOU ; Ze Lin LIU ; Dan Yu WANG ; Jian Xin GUO ; Li Ping PANG ; Qing Shu ZENG ; Xiao Hui SUO ; Wei Hua ZHANG ; Yuan Jun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2023;44(9):728-736
Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult
;
Humans
;
Adolescent
;
Imatinib Mesylate/adverse effects*
;
Incidence
;
Antineoplastic Agents/adverse effects*
;
Retrospective Studies
;
Pyrimidines/adverse effects*
;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
;
Treatment Outcome
;
Benzamides/adverse effects*
;
Leukemia, Myeloid, Chronic-Phase/drug therapy*
;
Aminopyridines/therapeutic use*
;
Protein Kinase Inhibitors/therapeutic use*
8.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
;
Female
;
Humans
;
Aged
;
Natriuretic Peptide, Brain
;
Simendan/therapeutic use*
;
Non-ST Elevated Myocardial Infarction
;
Heart Failure/drug therapy*
;
Peptide Fragments
;
Arrhythmias, Cardiac
;
Biomarkers
;
Prognosis
9.Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention.
Xiao-Tao WEI ; Tao LIU ; Zhi-Jun HE ; Jin-Peng LI ; Yuan SONG ; Jie CHEN ; Hai-Gang WANG ; Yuan-Xu HE ; Wei-Wei WANG ; Jing XIE
China Journal of Chinese Materia Medica 2023;48(7):1724-1730
Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.
Humans
;
Ulcer/therapy*
;
Medicine, Chinese Traditional
;
Beclin-1
;
Quality of Life
;
Wound Healing
;
Diabetes Complications
;
Autophagy
;
Diabetic Foot/drug therapy*
;
Diabetes Mellitus/genetics*
10.Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention.
Tao LIU ; Xiao-Tao WEI ; Zhi-Jun HE ; Jin-Peng LI ; Yuan SONG ; Jie CHEN ; Hai-Gang WANG ; Yuan-Xu HE ; Wei-Wei WANG
China Journal of Chinese Materia Medica 2023;48(7):1731-1738
Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.
Humans
;
Medicine, Chinese Traditional
;
Ulcer
;
Vascular Endothelial Growth Factor A/metabolism*
;
Diabetes Complications/drug therapy*
;
Wound Healing/physiology*
;
Diabetes Mellitus

Result Analysis
Print
Save
E-mail