1.Advancement of functional peptides: Promising candidates for antituberculosis therapeutics
Bojie LIN ; Siqi LIN ; Jiayi YANG ; Xuanyu YANG ; Shuhui WANG ; Yuting LIU ; Qianqian ZHANG ; Junfa XU ; Jiang PI ; Fen YANG
Science of Traditional Chinese Medicine 2026;4(1):24-32
Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis, is primarily airborne and remains a global health problem, especially in resource-limited countries and regions. The emergence of drug resistance in M. tuberculosis has rendered the existing means ineffective in the treatment of TB. Therefore, research in new therapeutic directions has become imperative. In this review, we outline functional peptides in terms of the mechanisms of action, anti-TB attempts, advantages and disadvantages, and latest advances, aiming to analyze the research progress in anti-TB peptides. Furthermore, we investigate the potential applications of bioactive compounds found in traditional Chinese Medicine within the context of peptides.
2.Endoscopic-assisted median nerve decompression combined with one-stage tendon transfer for reconstruction of thumb abduction in treatment of severe carpal tunnel syndrome.
Jiaxing SUI ; Yong YANG ; Zhenzhong WANG ; Xingjian HUANG ; Xuanyu JIANG ; Lihui ZHANG ; Haiyang LI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(12):1510-1515
OBJECTIVE:
To investigate the effectiveness of endoscopic-assisted median nerve decompression with one-stage extensor indicis proprius (EIP) tendon transfer for reconstruction of thumb abduction in patients with severe carpal tunnel syndrome (CTS).
METHODS:
The clinical data of 12 patients with severe CTS who met the selection criteria between December 2019 and December 2024 were retrospectively analyzed. There were 2 males and 10 females with an average age of 55.4 years ranging from 35 to 67 years. The symptom duration of CTS was 12-120 months (mean, 48.7 months) and the thenar muscle atrophy duration was 6-48 months (mean, 13.4 months). The median nerve was released with the help of endoscope, and the EIP tendon was transferred to reconstruct the abduction function of the thumb. The operation time and complications were recorded. Two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, and pinch force of the thumb were measured and compared before operation and at last follow-up, and the effectiveness was evaluated by Kapandji score and Disabilities of the Arm, Shoulder and Hand (DASH) score. The satisfaction of the operation was evaluated at last follow-up.
RESULTS:
All surgeries were successfully completed with a mean operation time of 54 minutes (range, 45-68 minutes). All patients were followed up 6-50 months, with an average of 15.3 months. There was no complications such as wound infection, scar pain of wrist, or tendon rupture of transposition, and there were 3 cases of mild limitation of finger extension in the donor site of index finger. At last follow-up, two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, Kapandji score, and DASH score were significantly better than those before operation ( P<0.05), but there was no significant difference in thumb pinch force between pre- and post-operation ( P>0.05). The evaluation of surgical satisfaction showed that 7 cases were very satisfied and 5 cases were satisfied.
CONCLUSION
The combination of endoscopic-assisted median nerve decompression and one-stage EIP tendon transfer effectively improves hand function and quality of life in patients with severe CTS by restoring thumb abduction and alleviating neurological symptoms.
Humans
;
Tendon Transfer/methods*
;
Male
;
Middle Aged
;
Carpal Tunnel Syndrome/physiopathology*
;
Female
;
Decompression, Surgical/methods*
;
Aged
;
Adult
;
Thumb/physiopathology*
;
Endoscopy/methods*
;
Retrospective Studies
;
Median Nerve/surgery*
;
Treatment Outcome
;
Plastic Surgery Procedures/methods*
3.Phorcides analytic engine-assisted corneal topography-guided personalized LASIK for the treatment of myopia and astigmatism
Xuanyu QIU ; Xindi WANG ; Yimeng FAN ; Zhao LIU ; Shengjian MI ; Li QIN
International Eye Science 2025;25(6):1020-1025
AIM: To observe the clinical outcomes of Phorcides analytic engine-assisted topography-guided personalized laser assisted in situ keratomileusis(LASIK)for the treatment of myopia and astigmatism in virgin eyes with the refractive astigmatism significantly deviating from corneal topography.METHODS: Retrospective clinical study. A total of 32 cases(42 eyes)with myopia and astigmatism that received corneal topography-guided personalized LASIK in the Ophthalmology Refractive Surgery Center of the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to March 2021 were selected. The uncorrected distance visual acuity(UDVA), best corrected distance visual acuity(CDVA), refractive state and aberrations before and at 6 mo after surgery were recorded.RESULTS: There were 15 males and 17 females, with an age of 23.00(18.00, 29.25)years old; preoperative sphere was -5.75(-6.25, -4.00)D, and cylinder was -0.75(-1.38, -0.25)D. At 6 mo postoperatively, the UDVA exceeded the preoperative CDVA in 19 eyes(45%). The spherical equivalent(SEQ)of all eyes(100%)was -0.50 to +0.50 D at 6 mo postoperatively, and the postoperative SEQ of 23 eyes(55%)was -0.13 to +0.13 D. There were 33 eyes(79%)had a postoperative astigmatism ≤ 0.25 D, the target-induced astigmatism(TIA)was 0.94±0.96 D, and the surgically induced astigmatism(SIA)was 0.94±0.86 D, with no statistical significance between TIA and SIA(P>0.05). The astigmatism axial deviation ranged from -5° to +5° in 33 eyes(79%)at 6 mo postoperatively. Compared to pre-operation, the total higher-order aberrations and spherical aberrations within the central 6 mm diameter of the anterior corneal surface increased at 6 mo postoperatively(Z=-3.778, P<0.001; Z=-4.929, P<0.001); the postoperative coma aberrations had no change(Z=-1.763, P=0.078); the postoperative trefoil aberrations decreased(Z=-2.490, P=0.013). Compared to pre-operation, the Strehl ratio of the anterior corneal surface increased significantly at 6 mo after surgeries(t=-5.401, P=0.013).CONCLUSION: Using the Phorcides analytic engine to assist topography-guided personalized LASIK for the treatment of myopia and astigmatism in virgin eyes with the refractive astigmatism significantly deviating from topography-measured astigmatism can achieve good therapeutic effects. Postoperative UDVA exceeded preoperative CDVA in nearly half of the eyes, and the quality of postoperative corneal imaging was improved.
4.Distribution of pathogens isolated from patients with eczema and clinical laboratory test indexes of patients with TCM syndrome type of eczema
Hongye MA ; Xiang GAO ; Xiaoxia HUANG ; Xuanyu WANG ; Chunyan JIANG ; Honglin GUO
Chinese Journal of Nosocomiology 2025;35(18):2765-2769
OBJECTIVE To explore the differences in the clinical laboratory test indexes between the patients with two different TCM syndrome types of eczema(dampness-heat infiltration type and non-dampness-heat infiltration type)and observe the distribution and drug resistance rate of pathogens isolated from the skin lesions so as to pro-vide bases for syndrome differentiation and reasonable use of antibiotics.METHODS A total of 180 patients with eczema who were positive for bacterial culture of skin secretions and were treated in Beijing Hospital of Traditional Chinese Medicine from Jan.2021 to Dec.2023 were enrolled in the study and were divided into the dampness-heat infiltration group with 134 cases and the non-dampness-heat infiltration group with 46 cases.The data of clini-cal laboratory test indexes were collected from the two groups of patients,the secretion specimens were sampled from the skin lesion sites,the isolated pathogens were identified by VITEK 2 Compact automatic microorganism analysis system,and the drug susceptibility testing was performed.RESULTS The direct bilirubin level of the dampness-heat infiltration group was(3.99±1.62)umol/L,higher than(3.46±1.12)umol/L of the non-damp-ness-heat infiltration group(P<0.05),but both were in the normal range;there were no significant differences in other test indexes between the two groups.Totally 180 strains of pathogens were isolated from the 180 patients with eczema,156(86.67%)of which were gram-positive bacteria;Staphylococcus aureus(98 strains),Staphy-lococcus epidermidis(29 strains)and Staphylococcus haemolyticus(15 strains)were the predominant species of the gram-positive bacteria.The gram-negative bacteria accounted for 12.22%(22 strains).The drug resistance rate of the S.aureus strains to penicillin was up to 82.65%,and the isolation rate of methicillin-resistant Staphy-lococcus aureus(MRSA)was 12.24%(12/98);the drug resistance rates of the S.epidermidis strains to penicil-lin and erythromycin were 75.86%,and the drug resistance rate of the S.haemolyticus strains to erythromycin was 100.00%.CONCLUSIONS The gram-positive bacteria(dominated by the S.aureus)are dominant among the pathogens isolated from the skin lesion specimens of the eczema patients and are highly resistant to penicillin and erythromycin.The isolation rate of MRSA is relatuvely low.There is limited clinical significant difference in the direct bilirubin between the two groups.It is necessary to further explore more reliable indexes for syndrome dif-ferentiation.
5.Hypoxia characteristics and prognostic significance of glioblastoma MES-like subpopulation through multi-transcriptomics sequencing
Tao CHEN ; Fan YANG ; Shuai WANG ; Min LUO ; Zexuan YAN ; Caidie TANG ; Yun NING ; Sisi YANG ; Ruofei CAO ; Zhengbo LI ; Xuanyu FANG ; Xiaohong YAO
Journal of Army Medical University 2025;47(16):1904-1912
Objective To analyze the composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38~2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.
6.Efficacy and safety analysis of denosumab in the treatment of osteoporosis in elder female patients with type 2 diabetes mellitus
Huanjun WANG ; Lin LI ; Li HU ; Xuanyu DENG ; Guangpeng RUAN ; Yinzhen PI
Chinese Journal of Diabetes 2025;33(6):439-443
Objective To analyze the efficacy and safety of denosumab(DEN)in the treatment of type 2 diabetes mellius(T2DM)complicated with osteoporosis(OP).Methods The DEN's efficacy on bone metabolism and glucose metabolism in patients with T2DM and OP was retrospectively analyzed through a before-and-after self-controlled design.Forty-one T2DM patients combined with OP who were treated in The First Hospital of Changsha from January 2022 to December 2022 were selected.All patients were observed with subcutaneous injection of DEN 60 mg every 6 months for 12 months.The changes of HbA1c,FPG,bone metabolism indexes,25-hydroxyvitamin D[25(OH)D]and bone mineral density(BMD)of patients before and after DEN treatment were compared.The adverse reactions of DEN were recorded.Results After 12 months of treatment,25(OH)D,the BMD oflumbar vertebra(L1~4),left femoral neck and left hip were higher than before treatment(P<0.05),while the osteocalcin,β-collagen special series,parathyroid hormone and alkaline phosphatase were lower than before treatment(P<0.05),and the adverse reactions were reduced.Conclusions DEN can significantly improve bone metabolism in patients with T2DM and osteoporosis,increase BMD of lumbar spine and whole hip with fewer adverse reactions.
7.Ultrasound radiomics combined with machine learning for early diagnosis of seronegative hashimoto’s thyroiditis
Wenjun WU ; Chang LIU ; Shengsheng YAO ; Daming LIU ; Yuan LUO ; Yihan SUN ; Ting RUAN ; Mengyou LIU ; Li SHI ; Mingming XIAO ; Qi ZHANG ; Zhengshuai LIU ; Xingai JU ; Jiahao WANG ; Xiang FEI ; Li LU ; Yang GAO ; Ying ZHANG ; Liying GONG ; Xuanyu CHEN ; Wanli ZHENG ; Xiali NIU ; Xiao YANG ; Huimei CAO ; Shijie CHANG ; Zuoxin MA ; Jianchun CUI
Chinese Journal of Endocrine Surgery 2025;19(3):313-319
Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.
8.Spontaneous brain activity changes in post-stroke aphasia and post-stroke depression:a meta-analysis of resting state functional magnetic resonance imaging
Yuhang CHEN ; Yu'ai YANG ; Xuanyu LU ; Yuhang WANG ; Mengyuan ZHANG ; Zihan ZHANG ; Huiying WANG ; Jingling CHANG
Chinese Journal of Rehabilitation Theory and Practice 2025;31(10):1143-1155
Objective To analyze the respective abnormal brain regions and commonly altered brain regions of spontaneous brain ac-tivity in post-stroke aphasia(PSA)and post-stroke depression(PSD),and to explore the potential pathological mechanisms underlying single disease and comorbidity.Methods Literatures were retrieved from PubMed,Embase,Web of Science,Cochrane Library,CNKI,Wanfang data,VIP and SinoMed,from establishment to April 19th,2025.Resting-state functional magnetic resonance imaging(fMRI)studies were included if they focused on patients with PSA or PSD,with healthy controls(HC)serving as control group,and amplitude of low-frequency fluctuation(ALFF),fractional amplitude of low-frequency fluctu-ation(fALFF)and regional homogeneity(ReHo)were adopted as outcome indicator.Data regarding differential brain regions were extracted from the original studies,and a neuroimaging meta-analysis was conducted using SDM-PSI V6.23 beta.Results A total of 17 articles on PSA(339 patients and 351 HC)and five articles on PSD(102 patients and 149 HC)were included.The spontaneous brain activity in the left cerebellar area 9,right middle temporal gyrus and right insula was significantly higher in PSA patients than in HC(P<0.05),while activity in the right cerebellar area 6,left medial superior frontal gyrus(SFGmed),left middle frontal gyrus and right anterior cingulate/paracingulate gyrus was lower(P<0.05).For PSD,spontaneous brain activity was elevated in the right cuneus gyrus and right superior occipital gyrus compared to HC(P<0.05),while it was reduced in the left SFGmed and left inferior pa-rietal lobe(P<0.05).Additionally,spontaneous brain activity in the left medial superior frontal gyrus was lower in both diseases compared to HC(P<0.05).Conclusion The pathological mechanism of PSA may involve a pattern of right-sided compensatory hyperfunction and left-sided inhibitory damage within the language-related network,accompanied by cross-hemispheric synergistic activity of the cerebellum.The occurrence of PSD may be attributed to hyperactivity of the right occipital net-work,and functional inhibition involving the left inferior parietal lobe.The inhibition observed in the left SFG-med(MNI coordinates x=0,y=26,z=44)likely represents the language-emotion integration hub,mediating the co-occurrence of PSA and PSD.
9.Ultrasound radiomics combined with machine learning for early diagnosis of seronegative hashimoto’s thyroiditis
Wenjun WU ; Chang LIU ; Shengsheng YAO ; Daming LIU ; Yuan LUO ; Yihan SUN ; Ting RUAN ; Mengyou LIU ; Li SHI ; Mingming XIAO ; Qi ZHANG ; Zhengshuai LIU ; Xingai JU ; Jiahao WANG ; Xiang FEI ; Li LU ; Yang GAO ; Ying ZHANG ; Liying GONG ; Xuanyu CHEN ; Wanli ZHENG ; Xiali NIU ; Xiao YANG ; Huimei CAO ; Shijie CHANG ; Zuoxin MA ; Jianchun CUI
Chinese Journal of Endocrine Surgery 2025;19(3):313-319
Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.
10.Spontaneous brain activity changes in post-stroke aphasia and post-stroke depression:a meta-analysis of resting state functional magnetic resonance imaging
Yuhang CHEN ; Yu'ai YANG ; Xuanyu LU ; Yuhang WANG ; Mengyuan ZHANG ; Zihan ZHANG ; Huiying WANG ; Jingling CHANG
Chinese Journal of Rehabilitation Theory and Practice 2025;31(10):1143-1155
Objective To analyze the respective abnormal brain regions and commonly altered brain regions of spontaneous brain ac-tivity in post-stroke aphasia(PSA)and post-stroke depression(PSD),and to explore the potential pathological mechanisms underlying single disease and comorbidity.Methods Literatures were retrieved from PubMed,Embase,Web of Science,Cochrane Library,CNKI,Wanfang data,VIP and SinoMed,from establishment to April 19th,2025.Resting-state functional magnetic resonance imaging(fMRI)studies were included if they focused on patients with PSA or PSD,with healthy controls(HC)serving as control group,and amplitude of low-frequency fluctuation(ALFF),fractional amplitude of low-frequency fluctu-ation(fALFF)and regional homogeneity(ReHo)were adopted as outcome indicator.Data regarding differential brain regions were extracted from the original studies,and a neuroimaging meta-analysis was conducted using SDM-PSI V6.23 beta.Results A total of 17 articles on PSA(339 patients and 351 HC)and five articles on PSD(102 patients and 149 HC)were included.The spontaneous brain activity in the left cerebellar area 9,right middle temporal gyrus and right insula was significantly higher in PSA patients than in HC(P<0.05),while activity in the right cerebellar area 6,left medial superior frontal gyrus(SFGmed),left middle frontal gyrus and right anterior cingulate/paracingulate gyrus was lower(P<0.05).For PSD,spontaneous brain activity was elevated in the right cuneus gyrus and right superior occipital gyrus compared to HC(P<0.05),while it was reduced in the left SFGmed and left inferior pa-rietal lobe(P<0.05).Additionally,spontaneous brain activity in the left medial superior frontal gyrus was lower in both diseases compared to HC(P<0.05).Conclusion The pathological mechanism of PSA may involve a pattern of right-sided compensatory hyperfunction and left-sided inhibitory damage within the language-related network,accompanied by cross-hemispheric synergistic activity of the cerebellum.The occurrence of PSD may be attributed to hyperactivity of the right occipital net-work,and functional inhibition involving the left inferior parietal lobe.The inhibition observed in the left SFG-med(MNI coordinates x=0,y=26,z=44)likely represents the language-emotion integration hub,mediating the co-occurrence of PSA and PSD.

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