1.Pathogenesis and Syndrome Differentiation Treatment of Heart Failure Based on "Spleen-mitochondria" and Theory of "Dampness, Turbidity, Phlegm, and Fluid-related Diseases"
Rui ZHANG ; Fuyun JIA ; Jingshun YAN ; Xuan LIU ; Yadong WANG ; Yinan MA ; Yan LIU ; Qiang XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):265-274
Guided by Academician Zhang Boli's theory of "dampness, turbidity, phlegm, and fluid-related diseases",this paper elaborated on the pathogenesis and syndrome differentiation treatment of heart failure from the perspective of the "spleen-mitochondria". It analyzed the essential similarities between "spleen-mitochondria" and "dampness, turbidity, phlegm, and fluid-related diseases", as well as their close association with the onset of heart failure. Furthermore,it explored the connection between spleen function and mitochondrial function in traditional Chinese medicine (TCM),positing that the spleen's role in transportation and transformation is analogous to mitochondrial material metabolism and energy conversion,with spleen deficiency closely related to mitochondrial dysfunction. It thus concluded that mitochondrial material metabolism and energy conversion represent the microscopic essence of the spleen's role in transportation and transformation,and mitochondrial dysfunction is a contributing factor to pathological products like dampness and turbid phlegm,which are closely associated with the occurrence of heart failure. The four elements of dampness,turbidity,phlegm,and fluid are a series of related symptoms resulting from abnormal fluid transportation and transformation,serving as both factors in the onset of heart failure and the core pathological basis for its deterioration. Therefore,during the treatment of heart failure,it is essential to regulate mitochondrial function. Early intervention should focus on eliminating dampness and turbidity to improve mitochondrial function and restore normal energy metabolism. In the middle and late stages,emphasis should be placed on resolving phlegm,promoting blood circulation,warming Yang,and reducing water retention to alleviate mitochondrial damage and improve cardiac function. Supporting Qi and strengthening the spleen should be a continuous approach,and treatment should be adjusted to enhance mitochondrial function and stabilize the condition,thereby improving prognosis. This paper discussed the role of the spleen and mitochondria in the pathogenesis of heart failure,examined the evolution of heart failure mechanisms from the perspective of dampness, turbidity, phlegm, and fluid-related diseases,and proposed a phased treatment strategy. It enriched the theory of dampness, turbidity, phlegm, and fluid-related diseases and offered new strategies for heart failure treatment. However,in practical application,TCM strategies for treating heart failure need to be integrated with modern medical approaches to provide a more solid scientific foundation for treatment.
2.Therapeutic Effect of Wenweishu Granules on Functional Dyspepsia Rats with Spleen-stomach Deficiency Cold Syndrome Based on Bioinformatics Analysis and Experimental Validation
Xinyu YANG ; Xiaoyi JIA ; Zihua XUAN ; Shuangying GUI ; Yanfang WU ; Yuhan MA ; Qin RUAN ; Jia ZHENG ; Zhiyong JIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):30-40
ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule (WWSG) on functional dyspepsia (FD) with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology, molecular docking, and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP). Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group, low-, medium-, and high-dose WWSG groups (2.0, 4.0, 8.0 g·kg-1), a domperidone group (3.0 mg·kg-1), a Fuzi Lizhong pillwan (0.8 g·kg-1), and a normal control group (n=10 per group). Drugs were administered once daily by gavage for 14 consecutive days. After treatment, body weight, symptom scores, and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin (HE) staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and Western blot were performed to assess stem cell factor (SCF) and receptor tyrosine kinase (c-Kit) protein expression in gastric tissues. ResultsA total of 305 drug targets, 1 140 disease targets, and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins (binding energy<-5.1 kcal·mol-1). Compared with the normal group, model rats exhibited slower weight gain (P<0.05), reduced gastric emptying and intestinal propulsion (P<0.01), mild gastric mucosal shedding, duodenal inflammatory cell infiltration, decreased levels of gastrin (GAS), 5-hydroxytryptamine (5-HT), and vasoactive intestinal peptide (VIP) (P<0.05, P<0.01), and elevated somatostatin (SS) expression (P<0.05, P<0.01). WWSG treatment ameliorated weight gain, symptom scores, and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion, upregulated GAS, 5-HT, and VIP, and downregulated SS expression in serum and tissues (P<0.05, P<0.01). Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group (P<0.05, P<0.01), which was reversed by WWSG intervention (P<0.05). ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats, potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.
3.Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, brain-dead human recipient.
Shuaijun MA ; Ruochen QI ; Shichao HAN ; Zhengxuan LI ; Xiaoyan ZHANG ; Guohui WANG ; Kepu LIU ; Tong XU ; Yang ZHANG ; Donghui HAN ; Jingliang ZHANG ; Di WEI ; Xiaozheng FAN ; Dengke PAN ; Yanyan JIA ; Jing LI ; Zhe WANG ; Xuan ZHANG ; Zhaoxu YANG ; Kaishan TAO ; Xiaojian YANG ; Kefeng DOU ; Weijun QIN
Chinese Medical Journal 2025;138(18):2293-2307
BACKGROUND:
The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation.
METHODS:
We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation.
RESULTS:
The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient.
CONCLUSIONS
5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods*
;
Kidney Transplantation/methods*
;
Heterografts/pathology*
;
Immunoglobulins, Intravenous/administration & dosage*
;
Graft Survival/immunology*
;
Humans
;
Animals
;
Sus scrofa
;
Graft Rejection/prevention & control*
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Kidney/pathology*
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Gene Editing
;
Species Specificity
;
Immunosuppression Therapy/methods*
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Plasma Exchange
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Brain Death
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Biopsy
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Male
;
Aged
4.Diagnostic and treatment strategies for testicular torsion.
Qing-Song MENG ; Wan-Ze ZHANG ; Ming ZHANG ; Jiang-Hua JIA ; Xin WANG ; Wan-Li MA ; Yao-Hua WANG ; Ya-Xuan WANG
National Journal of Andrology 2025;31(3):222-225
OBJECTIVE:
To investigate the differences between high-frequency ultrasound-guided manual detorsion combined with surgery (MD+S) and surgery alone in the treatment of testicular torsion, and to provide some new evidence for the timely diagnosis and treatment of the disease.
METHODS:
We retrospectively analyzed the clinical data on 134 cases of unilateral testicular torsion within 48 hours treated in our hospital by MD+S or by surgery alone from January 2015 to May 2022. We statistically analyzed the age distribution, and duration and degrees of testicular torsion, followed by comparison between the two groups.
RESULTS:
In the 134 cases, the median age of onset was 15 (13-19) years old, the median onset-to-visit time was 15 (8-25) hours, and the median degree of torsion was 360° (180°-1080°). Of the total number of patients, 21 underwent testicular excision and the other 113 were treated with the testis preserved, with no statistically significant difference in age distribution between the two groups (P>0.05), and a higher rate of testis resection in those with longer duration and greater angle of torsion (P<0.05). Totally, 33 of the patients were assigned to the MD+S group and 101 to the surgery alone group. According to the actual clinical conditions and excluding those with torsion time longer than 24 hours and torsion angle greater than 720 °, 28 of the patients underwent ultrasound-guided MD+S (with 1 case of testis resection, 3.6%), and 68 received surgery alone (with 7 cases of testis resection, 10.3%). The rate of testis resection was higher in the surgery alone than that in the MD+S group, but with no statistically significant difference between the two groups (P>0.05), which was considered to be related to the small sample size in this study.
CONCLUSION
The popularization of testicular torsion knowledge can shorten the onset-to-visit time, and reasonable manual detorsion before emergency surgery can reduce the rate of testis resection.
Humans
;
Male
;
Spermatic Cord Torsion/therapy*
;
Retrospective Studies
;
Adolescent
;
Young Adult
;
Ultrasonography
;
Testis/surgery*
;
Adult
5.Effects of Quorum Sensing Molecules on The Immune System
Wen-Min MA ; Xuan-Qi CHEN ; Hong-Xia MA ; Wen-Hui ZHANG ; Ling-Cong KONG ; Yu-Jia ZHOU ; Yuan-Yuan HU ; Yu JIA
Progress in Biochemistry and Biophysics 2024;51(11):2853-2867
In recent years, the development of host-acting antibacterial compounds has gradually become a hotspot in the field of anti-infection. Through research on the interaction mechanism between hosts and pathogenic bacteria, it has been found that the immune system is one of the key targets of host-acting antibacterial compounds. There is a communication system called the quorum sensing system in microorganisms, which mainly adjusts the structure of multi-microbial community and coordinates the group behavior. When the quorum sensing molecules secreted by microorganisms reach a threshold concentration, the quorum sensing system is activated and the overall gene expression of the microorganism is changed. In addition to regulating the density of microorganisms, quorum sensing molecules can also act as a link between pathogenic microorganisms and hosts, entering the host immune system and playing a role in affecting the morphological structure of immune cells, secreting cytokines, and inducing apoptosis, leading to host immune injury and causing host immune dysfunction.The key mechanism of 3-oxo-C12-HSL and other acyl-homoserine lactone (AHL) molecules in the innate immune system has been extensively studied. The lipid solubility allows AHLs to pass through the plasma membrane of host immune cells easily and induce dissolution of lipid domains. Then, it acts through signaling pathways such as p38MAPK and JAK-STAT, further influencing the immune cell’s defense response to bacteria and potentially leading to cell apoptosis. Additionally, the human lactonase paraoxonase 2, which can degrade3-oxo-C12-HSL, has been found in macrophage. It acts as an immune regulator that promotes macrophage phagocytosis of pathogens and is hypothesized to have the ability to reduce bacterial resistance. The mechanism of quorum sensing molecules in the adaptive immune system is less studied, the current results suggest that 3-oxo-C12-HSL is closely related to the mitochondrial pathway in host immune cells. For example, 3-oxo-C12-HSL induces apoptosis of Jurkat cells by inhibiting the expression of three mitochondrial electron transport chain proteins; it can also trigger mitochondrial dysfunction and induce mast cell apoptosis through Ca2+ signaling.Among the quorum sensing molecules, the AHLs have the greatest impact on plant immune system. The different effects on plant resistance depends on the chain lengths of acyl groups in bacterial-produced AHLs. Short-chain AHLs (C4-HSL and C8-HSL) induce plant resistance to pathogenic bacteria mainly through the auxin pathway and jasmonic acid pathway. Long-chain AHL (3-oxo-C14-HSL) is commonly used in hosts against fungal pathogens by inducing stomata defense responses, and the reaction process is related to salicylic acid. Diffusible signal factor molecules also interfere with the stomatal immunity caused by pathogens. It may act through the formin nanoclustering-mediated actin assembly and MPK3 pathway to inhibit the innate immunity of Arabidopsis. In summary, AHLs induced different plant pathways and affects the plant-bacteria interactions to trigger plant immunity. As a quorum sensing molecule of fungi, farnesol has similar effects on host immunity as AHLs, such as stimulating cytokine secretion and activating an inflammatory response. It also plays a unique role on dendritic cell differentiation and maturation. In addition, studies have found that farnesol has a protective effect on autoimmune encephalomyelitis, which may be related to its effect on the composition of intestinal microorganisms of the host.Therefore, targeting the host immune system and quorum sensing molecules to develop antibacterial compounds can effectively inhibit the invasion of pathogens and subserve the host to resist the influence of pathogenic bacteria. This article will review the mechanism of host immune responses triggered by important quorum sensing molecules, aiming to explore the targets of host-acting antibacterial compounds and provide new directions for the prevention or treatment of causative infectious sources and the development of related drugs.
6.Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism: A case-control study
Yinjian YANG ; Chao LIU ; Jieling MA ; Xijie ZHU ; Jingsi MA ; Dan LU ; Xinxin YAN ; Xuan GAO ; Jia WANG ; Liting WANG ; Sijin ZHANG ; Xianmei LI ; Bingxiang WU ; Kai SUN ; Yimin MAO ; Xiqi XU ; Tianyu LIAN ; Chunyan CHENG ; Zhicheng JING
Chinese Medical Journal 2024;137(16):1965-1972
Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.
7.Development of low-oxygen mixed gas generator for pilot hypoxia testing
Lin-Xia LI ; Jia-Ling XU ; Guo-Yun MAO ; Yao-Xuan JI ; Jin MA ; Yun-Ying WANG
Chinese Medical Equipment Journal 2024;45(7):24-28
Objective To develop a low-oxygen mixed gas generator to make up for the deficiencies of low-pressure chambers and load-resistant hypoxia trainers during pilot hypoxia tolerance testing.Methods The device prepared the low-oxygen gas with the principle of gas separation,which was composed of a Sunsource OLF1100D-220AF air compressor,a SMC IDG75SAM4-03 filter,a buffer tank,an AIR Products PA3010 integrated assembly,a control box,sensors and regulators.The sensors included the pressure sensor,flow sensor,concentration sensor and dew point temperature sensor,and the control box consisted of a main control board,a power supply module,a transmission module,a communication module,a display and a housing.The embedded control software of the device was developed with KEIL 5 and C++.Results The device developed prepared the low-oxygen gas with the volume fraction being 4%to 18%and the maximum error of volume fraction being 0.05%,and the main components of the prepared gas met the technical requirements of medical oxygen as stipulated in GB 8982-2009 Oxygen supplies for medicine and aircraft breathing.Conclusion The low-oxygen gas prepared by the device has its volume fraction precisely controlled and can be used for hypoxia tolerance testing and acclimation training for pilots.[Chinese Medical Equipment Journal,2024,45(7):24-28]
8.Molecular epidemiological characteristics of human infection with avian influenza A(H7N9)virus in Xinjiang from 2014 to 2018
Zhen-Guo GAO ; Muti-Mahe ; Jun ZHAO ; Jia HUANG ; Xuan ZHANG ; Yuan CHEN ; Lina·Turxunbayi ; Quan-Xi LI ; Xin MA
Chinese Journal of Zoonoses 2024;40(8):774-781
This study was aimed at analyzing the molecular epidemiological characteristics of all 14 cases of human infection with avian influenza A(H7N9)virus in Xinjiang from 2014 to 2018,to provide a scientific basis for prevention,control,and treatment.The genomic sequence was obtained through high-throughput gene sequencing after nucleic acid extraction.Homolo-gy analysis,evolution analysis,mutation locus analysis,and homology modeling were performed in bioinformatics analysis software.The nucleotide homology and amino acid homology of the HA gene in 14 human infected H7N9 viruses were(97.39%-100%)and(98.38%-100%),respectively.The nucleotide homology of the NA gene and the amino acid homology ranged from 97.73%to 100%.All viruses were low pathogenic avian influenza viruses belonging to the Yangtze River Delta lin-eage and were divided into two subclades,which were most similar to the A/Hunan/02650/2016 vaccine strain.All HA pro-teins G186V and T160A were mutated;13 strains of Q226L were mutated;and none of the four key neuraminidase inhibitor resistance sites of NA protein were mutated.All sites of M2 protein S31N and V27A were mutated,all sites of PB1 protein T368V were mutated,and all sites of PA protein K356R were mutated.Xinjiang H7N9 virus exhibited double receptor bind-ing,and was resistant to amantadine drugs and sensitive to neuraminidase inhibitors,which may be used in early disease sta-ges.Strengthened monitoring and timely detection of avian in-fluenza virus genome changes will be critical for prevention and control,and formulation of countermeasures.
9.Correlation of environment temperature with the incidence of testicular torsion
Qing-Song MENG ; Jia-Xing DU ; Ming ZHANG ; Jiang-Hua JIA ; Xin WANG ; Peng ZHANG ; Wan-Li MA ; Ya-Xuan WANG ; Dong-Bin WANG ; Jin-Chun QI
National Journal of Andrology 2024;30(2):128-131
Objective:To explore the influence of environment temperature on the incidence of testicular torsion.Methods:We collected the clinical data on 172 cases of testicular torsion diagnosed in the Second Hospital of Hebei Medical University from De-cember 2013 to December 2020.According to the local environment temperature on the day of onset,we divided the patients into groups A(below 0℃),B(0-10℃),C(10-20℃)and D(above 20℃),and compared the incidence rates of testicular torsion among the four groups,followed by correlation analysis.Results:The incidence rate of testicular torsion was 12.8%(n=22)in group A,35.5%(n=61)in B,34.9%(n=60)in C and 16.9%(n=29)in D,the highest at 0-10℃ in group B,with sta-tistically significant difference among the four groups(x2=29.07,P<0.001).Spearman correlation analysis indicated that the inci-dence of testicular torsion was negatively correlated with the environment temperature(r=-0.261,P<0.01),with no statistically significant difference among different seasons(x2=5.349,P>0.05),but higher in autumn and winter than in the other two sea-sons.Conclusion:The incidence of testicular torsion is negatively correlated with the environment temperature,elevated when the temperature decreases,but has no statistically significant difference among different seasons,though relatively higher in autumn and winter.
10.Correlation of lipid metabolism-related single nucleotide polymorphisms with abnormal semen quality in men
Xuan LIU ; Yuan-Jing LI ; Yue-Jia LI ; Jia-Jie BI ; Jing MA ; Fang-Fang DAI ; Shu-Song WANG
National Journal of Andrology 2024;30(3):199-208
Objective:To explore the potential impact of lipid metabolism-related single nucleotide polymorphisms(SNP)on semen quality in men.Methods:We selected 284 semen samples from Xingtai Infertility Hospital and Hebei Human Sperm Bank collected between February and October 2023,33 from oligozoospermia(OS),97 from asthenozoospermia(AS)and 54 from oligoas-thenozoospermia(OAS)patients and the other 100 from normal men.We performed computer-assisted semen analysis(CASA)of the samples,extracted blood DNA and,using the Mass ARRAY? System,genotyped the target genes,determined the genotypes of 13 SNPs and compared their distribution,their correlation with BMI and semen quality in different groups.Results:The mutant homozygous(TT)genotype of the FADS2 rs2727270 gene seemed to be a risk factor for AS(OR=4.420,P=0.047),while the APOA2 rs5082-A allele and MC4R rs17782313 heterozygous(TC)genotype important protective factors for OS(OR=0.422 and 0.389;P=0.045 and 0.043,respectively).A significantly higher sperm concentration was found associated with the MC4R rs17782313 heter-ozygous(TC)genotype than with the homozygous(CC)genotype.Stratification analysis showed that the protective effect of the TC genotype was decreased with increased BMI and remained with the interaction of the rs5082 and rs17782313 genotypes.Conclusion:FADS2 rs2727270,APOA2 rs5082 and MC4R rs17782313 were significantly correlated with the risk of abnormal semen parameters.

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