1.Effect of Zuogui Wan and Yougui Wan on Mitochondrial Biogenesis in BMSCs Through PGC-1α/PPARγ
Ying YANG ; Xiuzhi FENG ; Yiran CHEN ; Zhimin WANG ; Xian GUO ; Yanling REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):28-36
ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form", this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells (BMSCs) by mediating peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and peroxisome proliferators-activated receptor γ (PPARγ), providing theoretical support for the prevention and treatment of postmenopausal osteoporosis (PMOP) using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group, Zuogui Wan (ZGW) group, Yougui Wan (YGW) group, and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) method, and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ, CCAAT/enharcer-binding protein (C/EBP)α, C/EBPβ, lipoprotein lipase (LPL) protein, brown adipose tissue-related (BAT) proteins PGC-1α, uncoupcing protein 1 (UCP1), PR domdin-containing protein 16 (PRDM16), mitochondrial biogenesis-related PGC-1α, nuclear respiratory factor 1 (Nrf1), nuclear factor E2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). The expression of adipogenesis-related factors PPARγ, C/EBPα, C/EBPβ, LPL genes, and the copy number of cytochrome B (CytoB mtDNA) gene was detected using real-time polymerase chain reaction (Real-time PCR). Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group, the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed, and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ, C/EBPα, C/EBPβ, and LPL were significantly downregulated (P<0.01), while those of the BAT-related factors PGC-1α, UCP1, PRDM16 were significantly upregulated (P<0.01). The number of mitochondria increased, accompanied by reduced swelling. The double membrane and cristae structure were clear, and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased (P<0.01). The protein expression levels of mitochondrial biogenesis-related PGC-1α, Nrf1, Nrf2, and TFAM in each treatment group were significantly increased (P<0.01). ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.
2.Application of polyetheretherketone rod semi-rigid pedicle screw internal fixation in lumbar non-fusion surgery
Tao LIU ; Xing YU ; Jian-Bin GUAN ; Yong-Dong YANG ; He ZHAO ; Ji-Zhou YANG ; Yi QU ; Feng-Xian WANG ; Ding-Yan ZHAO ; Zi-Yi ZHAO
China Journal of Orthopaedics and Traumatology 2024;37(7):676-683
Objective To investigate the effect of Polyetheretherketone(PEEK)rod semi-rigid pedicle screw fixation sys-tem in lumbar spine non-fusion surgery.Methods A total of 74 patients with tow-level lumbar degenerative diseases who un-derwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group.In the PEEK rod group,there were 34 patients,including 13 males and 21 females,aged from 51 to 79 years old with an average of(62.4±6.8)years old;There were 1 patient of L1-L3 segments,7 patients of L2-L4 segments,20 patients of L3-L5 segments and 6 pa-tients of L4-S1 segments.In the titanium rod group,there were 40 patients,including 17 males and 23 females,aged from 52 to 81 years old with an average of(65.2±7.3)years old;There were 3 patient of L1-L3 segments,11 patients of L2-L4 segments,19 patients of L3-L5 segments and 7 patients of L4-S1 segments.The general conditions of operation,such as operation time,intraoperative blood loss,postoperative drainage was recorded.The visual analogue scale(VAS)for low back pain and Os-westry disability index(ODI)were compared in preoperatively and postoperatively(3 months,12 months and last follow-up)between two groups.The change of range of motion(ROM)was observed by flexion and extension x-ray of lumbar Results All patients successfully completed the operation.The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6)months.The operative time(142.2±44.7)min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group[(160.7±57.3)min、(212.8±85.4)ml](P<0.05).There was no significant differences in postoperative drainage between the two groups(P>0.05).At the final follow-up visit,in PEEK group and titanium group VAS of low back pain[(0.8±0.4)points vs(1.0±0.5)points],VAS for leg pain[(0.7±0.4)points vs(0.8±0.5)points]and ODI[(9.8±1.6)%vs(12.1±1.5)%]were compared with preoperative[(5.8±1.1)points vs(6.0±1.1)points],[(7.2±1.7)points vs(7.0±1.6)points],[(68.5±8.9)%vs(66.3±8.2)%]were significantly different(P<0.05).There was no significant difference in VAS scores between the two groups at each postoperative time point(P>0.05).At 3 months after surgery,there was no difference in ODI between the two groups(P>0.05).There were significant differences in ODI between PEEK group and titanium rod group at 12 months[(15.5±2.1)%vs(18.4±2.4)%]and at the last follow-up[(9.8±1.6)%vs(12.1±1.5)%](P<0.05).The total range of motion(ROM)of lumbar decreased in both groups after surgery.At 12 months after surgery and the last follow-up,the PEEK group compared with the titanium rod group,the total range of motion of lumbar was statistically significant(P<0.05).The range of motion(ROM)of the fixed segments decreased in both groups after surgery.The ROM of the fixed segments in PEEK group decreased from(9.5±4.6)° to(4.1±1.9)° at the last follow-up(P<0.05),which in the titanium rod group was de-creased from(9.8±4.3)°to(0.9±0.5)° at the last follow-up(P<0.05).The range of motion(ROM)of upper adjacent segment increased in both groups,there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up,(P<0.05).There was no screw loosening and broken rods in both groups during the follow-up period.Conclusion The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment,showing comparable short-term clinical efficacy to titanium rod fu-sion.PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degener-ative diseases,and its long-term efficacy needs further follow-up observation.
3.Quality evaluation of Yanyangke Mixture
Xiao-Lian LIANG ; Xiong-Bin GUI ; Yong CHEN ; Zheng-Teng YANG ; Jia-Bao MA ; Feng-Xian ZHAO ; Hai-Mei SONG ; Jia-Ru FENG
Chinese Traditional Patent Medicine 2024;46(6):1781-1787
AIM To evaluate the quality of Yanyangke Mixture.METHODS The HPLC fingerprints were established,after which cluster analysis,principal component analysis and partial least squares discriminant analysis were performed.The contents of liquiritin,rosmarinic acid,sheganoside,irisgenin,honokiol,monoammonium glycyrrhizinate,irisflorentin,isoliquiritin and magnolol were determined,the analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX SB-C18 column(5 μm,250 mmx4.6 mm),with the mobile phase comprising of 0.1%phosphoric acid-acetonitrile flowing at 1 mL/min in a gradient elution manner,and multi-wavelength detection was adopted.RESULTS There were ten common peaks in the fingerprints for twelve batches of samples with the similarities of more than 0.9.Various batches of samples were clustered into three types,three principal components displayed the acumulative variance contribution rate of 87.448%,peaks 5、14(honokiol),3(liquiritin),11(monoammonium glycyrrhizinate)and 15(asarinin)were quality markers.Nine constituents showed good linear relationships within their own ranges(r>0.999 0),whose average recoveries were 98.5%-103.6%with the RSDs of 0.92%-1.7%.CONCLUSION This stable and reliable method can provide a basis for the quality control of Yanyangke Mixture.
4.Establishment of primary breast cancer cell line as new model for drug screening and basic research
Xian HAO ; Jianjun HUANG ; Wenxiu YANG ; Jinting LIU ; Junhong ZHANG ; Yubei LUO ; Qing LI ; Dahong WANG ; Yuwei GAO ; Fuyun TAN ; Li BO ; Yu ZHENG ; Rong WANG ; Jianglong FENG ; Jing LI ; Chunhua ZHAO ; Xiaowei DOU
China Oncology 2024;34(6):561-570
Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.
5.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
6.Clinical trial of different courses of caffeine citrate in the treatment of very low birth weight infants
Yan-Feng ZHAO ; Fei YANG ; Xiao-Mei ZHOU ; Lin YE ; Xiao-Wen CHANG ; Xian-Li YE ; Yan WANG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2325-2328
Objective To compare the efficacy and safety of different courses of caffeine citrate injection in the treatment of very low birth weight infants.Methods Very low birth weight infants were divided into long course group and routine course according to cohort method.2 groups of children were given intravenous infusion of caffeine citrate injection loading dose(20 mg·kg-1)within 3 days after birth,and the dose was maintained at 5 mg·kg-1 after 24 hours(qd).In the long course group,caffeine citrate injection was used to correct gestational age>34 weeks,and in the routine course,caffeine citrate injection was used to correct gestational age 33-34 weeks.The use of caffeine citrate injection,clinical efficacy,neonatal behavioral neurological scale(NBNA)score and the occurrence of adverse drug reactions were compared between the two groups.Results 116 cases were included in this study,64 cases in the long course group and 52 cases in the routine course.After treatment,the total clinical effective rate of the long course group and the routine course was 92.19%and 94.23%,respectively,with no statistical significance(P>0.05).The total duration of caffeine citrate injection were(60.53±8.92)and(48.17±5.24)days,respectively;the corrected gestational age at withdrawal were(36.02±1.56)and(33.18±1.27)weeks,respectively.The corrected gestational age were(34.31±0.48)and(32.06±0.51)weeks;the milk volume were(32.69±2.14)and(23.85±1.69)mL,respectively,with statistical significance(all P<0.05).The starting age of caffeine citrate injection were(59.65±3.42)and(58.35±3.11)h in the long course group and the routine course,respectively,with no statistical significance(P>0.05).Before treatment,the NBNA score of the long course and routine courses were 36.49±6.78 and 35.58±4.22,respectively;the NBNA score of long course and conventional course after treatment were 43.25±6.88 and 44.12±7.42,respectively.Compared with before treatment,NBNA score in both groups were higher after treatment,with statistical significance(all P<0.05).There was no significant difference in NBNA score between the long course group and the routine course(P>0.05).The incidence of bronchopulmonary dysplasia(84.38%vs 51.92%)and decreased hemoglobin concentration(17.75%vs 5.77%)in the long course group were significantly higher than those in the routine course(all P<0.05).Conclusion Long-term use of caffeine citrate injection to correct gestational age>34 weeks has no significant effect on clinical treatment,neurological function and intellectual development of very low birth weight infants.
7.The Basis and Progress on Chemical Structure,Pharmacological Activity of Common Tibetan Medicine"Ye Ge Xing"
Annan YANG ; Yan FENG ; Zhifeng LI ; Yarong LI ; Yang XIAN ; Qi WANG ; Yulin FENG ; Guoyue ZHONG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(3):675-690
Objective Clarify the basis of the commonly used Tibetan medicinal material"YeGexing",the chemical structure and pharmacological activity were investigated,then provide a basis for standardizing clinical medication,quality control,and rational use of resources.Methods Using literature research;plant taxonomy identification summary of chemical composition investigation and pharmacological activity identification,combined with resource distribution,clinical use status investigation and analysis.Results Tibetan medicine"Yegexing"involved 7 species in 2 families,4 genera,that is Sambucus Linn.from Caprifoliaceae,Senecio L.,Synotis(C.B.Clarke)C.Jeffrey et Y.L.Chen,Saussurea DC.from Compositae.The earliest used"Yegexinggabao"or"white"should be Senecio dianthus.and Senecio solidagineus.in the literature;"Yegexingnabao"or"black"should be Saussurea epilobioides.and Sambucus adnate.;S.raphanifolius.(S.diversifolius.),S.chrysanthemoides.(S.laetus.).S.chinensis.are the main substitutes used in Yunnan,Gansu,and western Sichuan,and are commonly used in the market.YeGexing mainly contains terpenes,flavonoids,alkaloids,phenolic acids and other chemical components;YeGexing black is mainly used for"healing",white is mainly used for"anti-inflammatory",which corresponds to modern pharmacological research on anti-inflammatory,antioxidant,antibacterial and other activities.Conclution In view of the fact that the origin of"Yegexing"involves a variety of plants from different families and genera,"Yegexing"has become a collective name for these plant medicinal materials.According to the lextual results and the research progress on chemical structure and pharmacological activity,from the perspective of conducive to standardizing clinical medication,ensuring efficacy and quality of medicinal materials,its name and variety should be standardized as:"??????(???????????????????/)Yegexinggabao"(that is,the white one),the source is S.dianthus.(S.erythropappa.),S.solidagineus.(S.solidaginea.),S.raphalanifolius.(S.diversifolius.),S.chrysanthemoides.(S.laetus.);"(???????????????????????/)Yegexingnabao"(that is,the black one),the source is S.epilobioides.and S.adnata.and S.chinensis are independent medicines.We should strengthen the investigation of the resources and use status of substitutes in various places,the comparative research on the medicinal material basis and biological activity of different resource species,and standardize their varieties-names-bases to make rational use of their resources.
8.Analysis of Human Brain Bank samples from Hebei Medical University
Juan DU ; Shi-Xiong MI ; Yu-Chuan JIN ; Qian YANG ; Min MA ; Xue-Ru ZHAO ; Feng-Cang LIU ; Chang-Yi ZHAO ; Zhan-Chi ZHANG ; Ping FAN ; Hui-Xian CUI
Acta Anatomica Sinica 2024;55(4):437-444
Objective To understand the current situation of human brain donation in Hebei Province by analyzing the basic information of Human Brain Bank samples of Hebei Medical University in order to provide basic data support for subsequent scientific research.Methods The samples collected from the Human Brain Bank of Hebei Medical University were analyzed(from December 2019 to February 2024),including gender,age,cause of death,as well as quality control data such as postmortem delay time,pH value of cerebrospinal fluid and and RNA integrity number and result of neuropathological diagnosis.Results Until February 2024,30 human brain samples were collected and stored in the Human Brain Bank of Hebei Medical University,with a male to female ratio of 9∶1.Donors over 70 years old accounted for 53%.Cardiovascular and cerebrovascular diseases(36.67%)and nervous system diseases(23.33%)accounted for a high proportion of the death causes.The location of brain tissue donors in Shijiazhuang accounted for 90%donations,and the others were from outside the city.The postmortem delay time was relatively short,90%within 12 hours and 10%more than 12 hours.69.23%of the brain samples had RNA integrity values greater than 6.Cerebrospinal fluid pH values ranged from 5.8 to 7.5,with an average value of 6.60±0.45.Brain weights ranged from 906-1496 g,with an average value of(1210.78±197.84)g.Three apolipoprotein E(APOE)alleles were detected including five genotypes(ε2/ε3,ε2/ε4,ε3/ε3,ε3/ε4,ε4/ε4).Eleven staining methods related to neuropathological diagnosis had been established and used.A total of 12 cases were diagnosed as neurodegenerative diseases(including Alzheimer's disease,Parkinson's disease,multiple system atrophy,corticobasal degeneration and progressive supranuclear palsy,etc.),accounting for 40%donated brains.The comorbidity rate of samples over 80 years old was 100%.Conclusion The summary and analyses of the data of brain donors in the Human Brain Bank of Hebei Medical University can reflect the current situation of the construction and operation of the brain bank in Hebei Province,and it can also be more targeted to understand and identify potential donors.Our information can provide reference for the construction of brain bank and provides more reliable materials and data support for scientific research.
9.Differential expression analysis of the transcriptome for hurnan basal ganglia from normal donors and Parkinson's disease patients
Gao-Yu ZU ; Feng-Jiao LI ; Wei-Wei XIAN ; Yang-Yang GUO ; Bai-Cheng ZHAO ; Wen-Sheng LI ; Lin-Ya YOU
Acta Anatomica Sinica 2024;55(4):482-492
Objective To analyze the molecular markers of various nuclei in the human basal ganglia and the differentially expressed genes(DEGs)among different nuclei,gender,and Parkinson's disease(PD),followed by the biological function annotations of the DEGs.Methods Forty-five specimens of basal ganglia from 10 human postmortem brains were divided into control and PD groups,and the control group was further categorized into female and male groups.RNA from each sample was extracted for high-throughput transcriptome sequencing.Bioinformatic analysis was conducted to identify molecular markers of each nuclei in the control group,nuclei-specific,gender-specific,and PD-specific DEGs,followed by gene enrichment analysis and functional annotation.Results Sequencing analysis revealed top DEGs such as DRD1,FOXG1,and FAM183A in the caudate;SLC6A3,EN1,SLC18A2,and TH in the substantia nigra;MEPE and FGF10 in the globus pallidus;and SLC17A6,PMCH,and SHOX2 in the subthalamic nucleus.In them,putamen showed some overlapping DEGs with caudate,such as DRD1 and FOXG1.A significant number of DEGs were identified among different nuclei in the control group,with the highest number between caudate and globus pallidus(9321),followed by putamen and globus pallidus(6341),caudate and substantia nigra(6054),and substantia nigra and subthalamic nucleus(44).Gene enrichment analysis showed that downregulated DEGs between caudate and globus pallidus were significantly enriched in processes like myelination of neurons and cell migration.Upregulated DEGs between putamen and globus pallidus were enriched processes like chemical synaptic transmission and regulation of membrane potential,while downregulated DEGs were enriched in myelination and cell adhesion.Upregulated DEGs between caudate and substantia nigra were enriched in processes like chemical synaptic transmission and axonal conduction,while downregulated DEGs were enriched in myelination of neurons.Totally 468,548,1402,333,and 341 gender-specific upregulated DEGs and 756,988,2532,444,and 1372 downregulated DEGs were identified in caudate,putamen,substantia nigra,globus pallidus,and subthalamus nucleus.Gene enrichment analysis revealed upregulated DEGs mostly enriched in pathways related to immune response and downregulated DEGs in chemical synaptic transmission.At last,709,852,276,507,and 416 PD-specific upregulated DEGs and 830,2014,1218,836,and 1730 downregulated DEGs were identified in caudate,putamen,substantia nigra,globus pallidus,and subthalamus nucleus.Gene enrichment analysis revealed upregulated DEGs mostly enriched in apoptotic regulation and downregulated DEGs in chemical synaptic transmission and action potential regulation.Conclusion We identified and analysed the molecular markers of different human basal ganglia nuclei,as well as DEGs among different nuclei,different gender,and between control and PD.
10.Precirrhotic Primary Biliary Cholangitis with Portal Hypertension:Bile Duct Injury Correlate
Yi-Fan HU ; Shun-Xin LI ; Hong-Li LIU ; Zhi-Xiang DU ; Shuang-Shuang WANG ; Miao-Yang CHEN ; Li WANG ; Qing-Fang XIONG ; Yan-Dan ZHONG ; Du-Xian LIU ; Yong-Feng YANG
Gut and Liver 2024;18(5):867-876
Background/Aims:
The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH.
Methods:
This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients.
Results:
Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH.
Conclusions
Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

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