5.Application and clinical efficacy of red blood cell therapeutic apheresis in erythropoietic protoporphyria and hereditary hemochromatosis
Haoqiang LIU ; Caihan ZHAO ; Qing YUAN ; Lixia XIE ; Yong ZOU ; Ying LU
Chinese Journal of Blood Transfusion 2025;38(7):915-921
Objective: To explore the application and clinical efficacy of red blood cell therapeutic apheresis in erythropoietic protoporphyria (EPP) and hereditary hemochromatosis (HH). Methods: 1) The EPP patient was hospitalized twice for "abdominal pain, nausea, vomiting, and brown urine". One and two sessions of red blood cell exchange/therapeutic plasma exchange (RCE/TPE) were respectively performed during the two hospitalizations. During each session, one RCE with 6-8 units of leukoreduced RBCs and 3-4 TPE procedures with 1 800-2 000 mL of frozen plasma was conducted. Biochemical parameters were monitored before and after treatment. 2) The HH patient was hospitalized for “repeatedly elevated aminotransferases”. Erythrocytapheresis was performed once, removing 550 mL of red blood cells, and venous phlebotomy was conducted once every 2 months subsequently. Blood routine and ferritin levels were assessed before and after treatment. Results: 1) During the first hospitalization, the EPP patient was relieved of the abdominal pain and brown urine after therapeutic apheresis. The total bilirubin level decreased from 141.8 μmol/L on admission to 68.6 μmol/L at discharge, with a symptom remission duration of 10 months. During the second hospitalization, the EPP patient still had recurrent abdominal pain after therapeutic apheresis. He developed psychiatric symptoms and gastrointestinal bleeding subsequently, accompanied by elevated bilirubin levels. Liver function deteriorated and the patient went into the state of the end-stage liver disease (ESLD). 2) For the HH patient, the hemoglobin level prior to erythrocytapheresis and vein phlebotomy was 150-160 g/L, with the lowest value occurring two days after erythrocytapheresis, decreasing to 107 g/L. The ferritin level before erythrocytapheresis was 2 428.08 ng/mL and it declined gradually after theraphy, with the lowest value occurring two months after erythrocytapheresis, decreasing to 1 094 ng/mL. The ferritin level was 1 114 ng/mL two months following the first vein phlebotomy, however it increased to 1 472 ng/mL two months after the second vein phlebotomy. Conclusion: RCE/TPE may alleviate protoporphyrin liver disease and help patients with bridging liver transplantation before EPP developments to ESLD. For HH patients with significantly elevated ferritin levels, erythrocytapheresis reduces serum ferritin more quickly and maintains its level longer relative to phlebotomy.
6.Application and clinical efficacy of red blood cell therapeutic apheresis in erythropoietic protoporphyria and hereditary hemochromatosis
Haoqiang LIU ; Caihan ZHAO ; Qing YUAN ; Lixia XIE ; Yong ZOU ; Ying LU
Chinese Journal of Blood Transfusion 2025;38(7):915-921
Objective: To explore the application and clinical efficacy of red blood cell therapeutic apheresis in erythropoietic protoporphyria (EPP) and hereditary hemochromatosis (HH). Methods: 1) The EPP patient was hospitalized twice for "abdominal pain, nausea, vomiting, and brown urine". One and two sessions of red blood cell exchange/therapeutic plasma exchange (RCE/TPE) were respectively performed during the two hospitalizations. During each session, one RCE with 6-8 units of leukoreduced RBCs and 3-4 TPE procedures with 1 800-2 000 mL of frozen plasma was conducted. Biochemical parameters were monitored before and after treatment. 2) The HH patient was hospitalized for “repeatedly elevated aminotransferases”. Erythrocytapheresis was performed once, removing 550 mL of red blood cells, and venous phlebotomy was conducted once every 2 months subsequently. Blood routine and ferritin levels were assessed before and after treatment. Results: 1) During the first hospitalization, the EPP patient was relieved of the abdominal pain and brown urine after therapeutic apheresis. The total bilirubin level decreased from 141.8 μmol/L on admission to 68.6 μmol/L at discharge, with a symptom remission duration of 10 months. During the second hospitalization, the EPP patient still had recurrent abdominal pain after therapeutic apheresis. He developed psychiatric symptoms and gastrointestinal bleeding subsequently, accompanied by elevated bilirubin levels. Liver function deteriorated and the patient went into the state of the end-stage liver disease (ESLD). 2) For the HH patient, the hemoglobin level prior to erythrocytapheresis and vein phlebotomy was 150-160 g/L, with the lowest value occurring two days after erythrocytapheresis, decreasing to 107 g/L. The ferritin level before erythrocytapheresis was 2 428.08 ng/mL and it declined gradually after theraphy, with the lowest value occurring two months after erythrocytapheresis, decreasing to 1 094 ng/mL. The ferritin level was 1 114 ng/mL two months following the first vein phlebotomy, however it increased to 1 472 ng/mL two months after the second vein phlebotomy. Conclusion: RCE/TPE may alleviate protoporphyrin liver disease and help patients with bridging liver transplantation before EPP developments to ESLD. For HH patients with significantly elevated ferritin levels, erythrocytapheresis reduces serum ferritin more quickly and maintains its level longer relative to phlebotomy.
7.Treatment of MASLD from Intestinal Microbial-mitochondrial Interactions Based on "Spleen and Stomach-Xuanluo" Theory
Ran ZHAO ; Bingjiu LU ; Jingran SUN ; Jialian ZHENG ; Qing XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):220-227
Traditional Chinese medicine (TCM) has long recognized metabolism-associated fatty liver disease (MASLD). The Classic of Difficulties (Nan Jing) records that "the accumulation of the liver is called obese Qi". ZHANG Jingyue also stated, "People with spleen and stomach deficiency and weakness or imbalance often suffer from diseases of accumulation". According to syndrome differentiation of the Zang-fu organs, modern physicians generally believe that the key pathogenesis of MASLD lies in the deficiency of spleen and stomach functions. However, MASLD is a chronic and complex disease, and its pathological characteristics cannot be fully explained by a single Zang-Fu syndrome differentiation. The concepts of sweat pores and collateral vessels emerged as early as the Huangdi's Internal Classic (Huang Di Nei Jing), and later TCM scholars, based on the idea that "sweat pore is the gateway of collateral vessels" proposed the concept of Xuanluo (sweat pores-collateral vessels). Xuanluo refers to fine structures widely distributed throughout the human body, serving as hubs and channels that regulate the movement and distribution of Qi, blood, and body fluids. By linking the Zang-Fu organs with Xuanluo, a theoretical framework of Qi, blood, and body fluid circulation centered on the "spleen and stomach-Xuanluo" as a whole was established, providing a new perspective for analyzing the essential pathogenesis of MASLD. Combined with the mechanisms involved in the formation and progression of MASLD, the intrinsic correlations between TCM pathogenesis and modern microscopic mechanisms are further analyzed. Modern studies have shown that intestinal microbial dysbiosis and mitochondrial dysfunction are pathological mechanisms involved in the occurrence and development of MASLD, but few have discussed the two as an integrated system. Existing research has confirmed that intestinal microorganisms can affect mitochondrial energy metabolism and oxidative stress through their metabolites, leading to hepatic energy metabolism disorders, oxidative stress (OS), and inflammation, thereby promoting MASLD progression. Focusing on the correspondence between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion micro-pathological mechanism, it is proposed that the spleen and stomach share similarities with intestinal microorganisms in the generation of Qi, blood, and body fluids as well as in the regulation of Qi movement, while Xuanluo and mitochondria have commonalities in energy regulation. Moreover, harmonizing the spleen and stomach to ensure unobstructed Xuanluo is the key to maintaining the normal interaction mechanism between intestinal microorganisms and mitochondria. Based on the correlation between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion interaction, this paper reveals that the essence of MASLD pathogenesis lies in spleen and stomach dysfunction, specifically, failure of the spleen to ascend the clear and failure of the stomach to descend the turbid, resulting in insufficient transformation of Qi and blood, impaired nourishment of Xuanluo, stagnation of Qi and blood, and the long-term formation of phlegm and blood stasis in the liver. Furthermore, it explores the preventive and therapeutic effects of tonifying the spleen and stomach, dredging Xuanluo and collaterals, unblocking the bowels, and regulating Qi in the treatment of MASLD, thereby providing new insights for its prevention and therapy.
8.Study of lncRNA-miRNA-mRNA ceRNA regulatory network mediated by serum exosomes in coronary heart disease and prediction and experimental validation of potential target herbal medicines
Lu MA ; Lei YANG ; Huang DING ; Wan-Yu LI ; Wei TAN ; Yan-Ling LI ; Yan-Yan ZHANG ; Xiao-Dan LIU ; Zhao-Wen ZENG ; Chang-Qing DENG ; Wei ZHANG
Chinese Pharmacological Bulletin 2024;40(6):1153-1164
Aim To analyze serum exosome sequencing data from patients with coronary heart disease(CHD)and normal subjects by using bioinformatics-related methods to construct a competitive endogenous ln-cRNA-miRNA-mRNA(ceRNA)regulatory network,to mine the predicted potential Chinese medicines,and to perform preliminary validation of the biological processes and core Chinese medicines involved in the ceRNA network.Methods We used exoRbase data-base to obtain the expression matrix of differential genes,combined with the raw letter method to con-struct the ceRNA network,and performed GO analysis and KEGG analysis on the differential mRNAs in the network,and used COREMINE database to predict the biological processes and core target genes involved in the ceRNA network,and to screen the herbal medi-cines with potential therapeutic effects;AVECs oxida-tive damage cell model was constructed in vitro,and the cytoskeleton,tube-forming function,cell prolifera-tion,LDH leakage rate,ROS level and p-AKT,AKT,p-PI3K and AKT protein expression were examined to verify the action pathways and targets of the core Chi-nese medicine Salvia miltiorrhiza for the treatment of coronary heart disease.Results Compared with nor-mal subjects,395 mRNAs,80 miRNAs,60 lncRNA differential genes,and 80 miRNAs were predicted in serum exosomes of coronary heart disease,and the constructed ceRNA sub-network,mainly consisted of 21 lncRNAs,80 miRNAs,and 82 mRNAs;AKT1,VEGFA,IL1B and other genes in the network.The abnormally expressed mRNAs were involved in biologi-cal processes such as oxidative stress and signaling pathways such as PI3 K/Akt,and Dan Shen,Chuanx-iong and Panax notoginseng were most closely related to exosome-mediated biological processes and core genes in coronary heart disease.The active ingredients of tanshinone ⅡA,the core Chinese medicine,could pro-mote vascular endothelial cell proliferation,tube for-mation,skeleton formation and repair,reduce LDH leakage rate and ROS level,and promote the expres-sion of p-AKT and p-PI3K protein.Conclusion There is a complex ceRNA regulatory network trans-duction in coronary artery disease serum exosomes,and traditional Chinese medicine can be used to treat CHD through multi-target intervention,and Dan Shen,Chuanxiong and Panax notoginseng are expected to be candidate sources of traditional Chinese medicine,a-mong which the active ingredient of Dan Shen,tanshi-none ⅡA,activates PI3 K/Akt signaling pathway to play a protective role against oxidative stress-injured cells,and treats CHD.
9.Research progresses of endogenous vascular calcification inhibitor BMP-7
Xin ZHOU ; Lu XING ; Peng-Quan LI ; Dong ZHAO ; Hai-Qing CHU ; Chun-Xia HE ; Wei QIN ; Hui-Jin LI ; Jia FU ; Ye ZHANG ; Li XIAO ; Hui-Ling CAO
Chinese Pharmacological Bulletin 2024;40(7):1226-1230
Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.
10.Effects of tramadol hydrochloride preemptive analgesia in kyphoplasty of thoracolumbar osteoporotic fractures un-der local anesthesia
Guo-Qing LI ; Hua-Guo ZHAO ; Shao-Hua SUN ; Wei-Hu MA ; Hao-Jie LI ; Yang WANG ; Lian-Song LU ; Chao-Yue RUAN
China Journal of Orthopaedics and Traumatology 2024;37(6):560-564
Objective To explore preemptive analgesic effect of preoperative intramural tramadol injection in percutaneous kyphoplasty(PKP)of vertebrae following local anesthesia.Methods From August 2019 to June 2021,118 patients with thora-co lumbar osteoporotic fractures were treated and divided into observation group and control group,with 59 patients in each gruop.In observation group,there were 26 males and 33 females,aged from 57 to 80 years old with an average of(67.69±4.75)years old;14 patients on T11,12 patients on T12,18 patients on L1,15 patients on L2;tramadol with 100 mg was injected intramuscularly half an hour before surgery in observation group.In control group,there were 24 males and 35 females,aged from 55 to 77 years old with an average of(68.00±4.43)years old;19 patients on T11,11 patients on T12,17patients on L1,12 patients on L2;the same amount of normal saline was injected intramuscularly in control group.Observation indicators included operation time,intraoperative bleeding,visual analogue scale(VAS)evaluation and recording of preoperative(T0),intraoper-ative puncture(T1),and working cannula placement(T2)between two groups of patients,at the time of balloon dilation(T3),when the bone cement was injected into the vertebral body(T4),2 hours after the operation(T5),and the pain degree at the time of discharge(T6);adverse reactions such as dizziness,nausea and vomiting were observed and recorded;the record the patient's acceptance of repeat PKP surgery.Results All patients were successfully completed PKP via bilateral pedicle ap-proach,and no intravenous sedative and analgesic drugs were used during the operation.There was no significant difference in preoperative general data and VAS(T0)between two groups(P>0.05).There was no significant difference in operation time and intraoperative blood loss between the two groups(P>0.05).VAS of T1,T2,T3,T4 and T5 in observation group were all lower than those in control group(P<0.05),and there was no significant difference in T6 VAS(P>0.05).T6 VAS between two groups were significantly lower than those of T0,and the difference was statistically significant(P<0.05).There was no signifi-cant difference in incidence of total adverse reactions between two groups(P>0.05).There was a statistically significant differ-ence in the acceptance of repeat PKP surgery(P<0.05).Conclusion Half an hour before operation,intramuscular injection of tramadol has a clear preemptive analgesic effect for PKP of single-segment thoracolumbar osteoporotic fracture vertebral body under local anesthesia,which could increase the comfort of patients during operation and 2 hours after operation,and improve patients satisfaction with surgery.

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