Objective The study aimed to elucidate the evolution of the syndromes in Traditional Chinese Medicine(TCM)and TCM syndrome elements in different chronic stages of psoriasis vulgaris.Methods A database was constructed using electronic medical records collected from July 2019 to March 2024 from 1,049 patients with psoriasis vulgaris.The study used Sankey diagrams and network association graphs to analyze the evolution of TCM syndromes and their elements in patients at the different stages:initial diagnosis,progressive stage(Week 2-3),progressive stage(Week 4-5),skin lesion improvement stage(Week 6-7),and remission stage.The syndrome elements network was constructed using community detection algorithms,and the association rules between local skin lesion syndrome differentiation and overall syndrome differentiation were displayed using heatmaps.Results(ⅰ)Initial diagnosis.In the syndrome differentiation of local skin lesions,blood heat syndrome was the most common(79.79％);among the disease location of TCM syndrome elements(called"disease location"),liver was the most prevalent(35.62％);and among the pathological factors of TCM syndrome elements(called"pathological factors"),fire(heat)was the most common(75.48％).(ⅱ)Active stage(Week 2-3).In the syndrome differentiation of local skin lesions,blood heat syndrome remained the most prevalent(73.13％);among the disease location,liver was still the most prevalent(31.71％);and among the pathological factors,fire(heat)continued to be the most common(82.11％),while dampness(22.26％)and qi stagnation(8.39％)began to increase.(ⅲ)Active stage(Week 4-5).The syndrome differentiation of local skin lesions was dominated by blood heat syndrome(45.91％)and blood dryness syndrome(37.19％);among disease location,the interior was the most prevalent(15.25％);and among the pathological factors,fire(heat)remained the most common(50.66％),with an increase in yin deficiency(34.26％).(ⅳ)Skin lesion improvement stage(Week 6-7).In the syndrome differentiation of local skin lesions,both blood dryness syndrome(49.44％)and blood stasis syndrome(33.33％)increased;among the disease location,meridians increased most significantly and became the most prevalent(13.44％);and among the pathological factors,blood stasis increased most significantly and became the most prevalent(28.20％).(ⅴ)Remission stage.In the syndrome differentiation of local skin lesions,blood stasis syndrome became the primary(55.69％),while the percentage of blood dryness syndrome decreased(21.16％);meridians(25.71％)and blood stasis(62.34％)remained the most predominant syndrome elements related to disease location or pathological factors.Conclusion The overall pattern of TCM syndromes in psoriasis vulgaris evolved from excess to deficiency.From the initial diagnosis to the active phase(Week 2-3),heat syndrome dominated;during the active phase(Week 4-5),heat syndrome coexisted with damp syndrome or yin deficiency syndrome;changes in the syndrome element network were the most significant during the lesion improvement phase,with blood stasis gradually increasing and peaking during the remission phase.Blood stasis,dampness,and qi stagnation were pervasive throughout psoriasis vulgaris;qi stagnation and blood stasis may be the main elements causing further deterioration and prolonged course of the disease during the active phase in patients.

Objective To investigate the risk factors associated with prolonged hospitalization in patients diagnosed with diabetic foot ulcers(DFU),to develop a predictive model,and to conduct internal validation of the model.Methods The clinical data of DFU patients admitted to West China Hospital,Sichuan University between January 2012 and December 2022 were retrospectively collected.The subjects were randomly assigned to a training cohort and a validation cohort at a ratio of 7 to 3.Hospital stays longer than 75th percentile were defined as prolonged length-of-stay.A thorough analysis of the risk factors was conducted using the training cohort,which enabled the development of an accurate risk prediction model.To ensure robustness,the model was internally validated using the validation cohort.Results A total of 967 inpatients with DFU were included,among whom 245 patients were identified as having an extended length-of-stay.The training cohort consisted of 622 patients,while the validation cohort comprised 291 patients.Multivariate logistic regression analysis revealed that smoking history(odds ratio[OR]=1.67,95%confidence interval[CI],1.13 to 2.48,P=0.010),Wagner grade 3 or higher(OR=7.13,95%CI,3.68 to 13.83,P＜0.001),midfoot ulcers(OR=1.99,95%CI,1.07 to 3.72,P=0.030),posterior foot ulcers(OR=3.68,95%CI,1.83 to 7.41,P＜0.001),multisite ulcers(OR=2.91,95%CI,1.80 to 4.69,P＜0.001),wound size≥3 cm2(OR=2.00,95%CI,1.28-3.11,P=0.002),and white blood cell count(OR=1.11,95%CI,1.05 to 1.18,P＜0.001)were associated with an increased risk of prolonged length of stay.Additionally,a nomogram was constructed based on the identified risk factors.The areas under the receiver operating characteristic(ROC)curves for both the training cohort and the validation cohort were 0.782(95%CI,0.745 to 0.820)and 0.756(95%CI,0.694 to 0.818),respectively,indicating robust predictive performance.Furthermore,the calibration plot demonstrated optimal concordance between the predicted probabilities and the observed outcomes in both the training and the validation cohorts.Conclusion Smoking history,Wagner grade≥3,midfoot ulcers,posterior foot ulcers,multisite ulcers,ulcer area≥3 cm2,and elevated white blood cell count are identified as independent predictors of prolonged hospitalization.Therefore,it is imperative that clinicians conduct a comprehensive patient evaluation and implement appropriate diagnostic and therapeutic strategies to effectively shorten the length of stay for DFU patients.

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M). METHODS: A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus. RESULTS: Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion. CONCLUSION By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.
Humans ; Pregnancy ; Female ; Child ; Male ; Preimplantation Diagnosis ; East Asian People ; Semen ; Genetic Testing ; Muscular Atrophy, Spinal/genetics* ; Aneuploidy ; Blastocyst/pathology* ; High-Throughput Nucleotide Sequencing ; Spermatozoa

Objective To explore the characteristics of baseline inflammatory markers in diabetic foot patients and their relationship with the prognosis of diabetic foot ulcers.Methods The clinical data of diabetic foot patients(n=495)admitted to West China Hospital,Sichuan University since 2016 were retrospectively collected through the hospital electronic medical record system to analyze the characteristics of inflammatory markers and their relationship with the prognosis of diabetic foot ulcers.Results White blood cell count(WBC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),procalcitonin(PCT),and interleukin-6(IL-6)levels were significantly higher in patients defined as grade 4 on the Wagner Scale than those in patients defined as grade 0-3 on the Wagner Scale.Neutrophil percentage(NE％)was higher in Wagner grade-4 patients than those in Wagner grade-0 and grade-1 patients and higher in Wagner grade-3 patients than those in Wagner grade-0 patients.NE％,CRP,PCT,and IL-6 levels were positively correlated with the severity of diabetic foot,with the respective odds ratio(OR)at 95％confidence interval(CI)being 1.038(1.019-1.056),1.019(1.012-1.026),8.225(2.015-33.576),and 1.017(1.008-1.025).Using Wagner grade-0 patients as the reference,patients with higher WBC were more likely to progress to Wagner grade 2,3,and 4,with the respective OR(95％CI)values being 1.260(1.096-1.447),1.188(1.041-1.356),and 1.301(1.137-1.490);patients with higher ESR were more likely to progress to Wagner grade 3 and 4,with the respective OR(95％CI)values being 1.030(1.006-1.054)and 1.045(1.019-1.071).Baseline ESR(P=0.008),CRP(P=0.039),and IL-6(P=0.033)levels were lower in patients who had received antibiotics prior to their admission than those in patients who had not received antibiotics before admission.The levels of WBC,NE％,ESR,PCT,and IL-6 were lower in the full recovery group than those in the group of patients who did not respond to treatment.The higher the levels of NE％and IL-6,the worse the prognosis of diabetic foot ulcers became,with the respective OR(95％CI)values being 1.030(1.010-1.051)and 1.008(1.002-1.013).Conclusion The severity of diabetic foot ulcers increased with the rise in baseline levels of inflammatory markers.Elevated baseline NE％and IL-6 levels suggest a poor prognosis.Our findings suggest that early assessment of diabetic foot infection and standardized antibiotic therapy should be implemented to improve the prognosis.

Objective:To compare the difference of the ocular surface and efficacy of orthokeratology lenses wearing after using sodium hyaluronate eye drops, rewetting drops and saline solution.Methods:A randomized single-blind controlled trial was conducted.A total of 90 right eyes from 90 myopic patients were recruited from June 2017 to April 2018 in Hainan Eye Hospital.All the subjects received vision correction by orthokeratology lens, and were randomly divided into three groups by random number table method, with 30 eyes in each group.The sodium hyaluronate group was given preservative-free sodium hyaluronate eye drops (1 g/L), the rewetting drops group was given rewetting drops, and the saline solution group was given nonpreserved 0.9% NaCl.The vision, subjective refraction, corneal topography, non-invasive first tear film break-up time(NIKf-BUT) and fluorescein stain of corneal epithelium (FL) were detected before and 1 day, 1 week, 1 month, 3 months after the lens wearing.This study adhered to the Declaration of Helsinki and was approved by the institutional Ethical Committee Review Board of Hainan Eye Hospital.Results:The NIKf-BUT in the sodium hyaluronate group at 1 day, 1 week, 1 month and 3 months after wearing orthokeratology lens was (7.13±1.71), (6.61±1.49), (6.37±1.82) and (7.01±1.63) seconds, respectively, which was obviously higher than (6.32±1.71), (5.53±1.42), (5.57±1.50) and (6.17±1.63) seconds in the rewetting drops group at the corresponding time points and (6.36±1.58), (5.81±1.49), (5.74±1.77) and (6.28±1.53) seconds in the saline solution group at the corresponding time points (all at P<0.05). There was no statistically significant difference in FL score between the rewetting drops group and saline solution group at 1 day, 1 week, 1 month and 3 months after wearing the orthokeratology lens (all at P>0.05). Lower FL scores were observed in the sodium hyaluronate group compared to the the rewetting drops group and saline solution group after wearing the orthokeratology lens (all at P<0.05). No differences were found in uncorrected visual acuity, spherical equivalent and average K value among the groups (all at P>0.05). Conclusions:Compared with the rewetting drops and saline solution, the preservative-free sodium hyaluronate eye drops can stabilize the tear film and have less effect on corneal epithelium at the early stage of orthokeratology lens wearing.However, there is no significant difference in the improvement of visual acuity and the rate of corneal shaping.

Objective:To investigate the in vitro interaction between antifungals and tacrolimus against Fusarium solani. Methods:According to Clinical and Laboratory Standards Institute(CLSI) M27-Ed4 and M38-A3, 24 strains of Fusarium solani isolated from clinic were used to test the minimal inhibitory concentration (MIC) of the four antifungals.Chessboard microdilution method was used to evaluate the interaction of tacrolimus (FK506) combined with four antifungals in vitro.The study protocol was approved by the Ethics Committee of Hainan Eye Hospital (No.2017-006). Results:The MIC ranges of fluconazole, voriconazole, natamycin and amphotericin B against 24 strains of Fusarium were 64-256 μg/ml, 1-8 μg/ml, 2-8 μg/ml and 1-8 μg/ml, respectively.Tacrolimus combined with fluconazole, voriconazole, natamycin and amphotericin B had synergistic effects on 12.5% (3/24), 4.2% (1/24), 16.7% (4/24) and 29.2% (7/24) Fusarium, respectively.There were no antagonistic effect in this study. Conclusions:Fusarium is sensitive to natamycin in vitro and partly sensitive to amphotericin B and voriconazole.Synergistic effects exist in few strains of Fusarium but no antagonistic effect.

To compare the clinical features and the heterogeneity of macrophages in different clinical phenotypes of chronic obstructive pulmonary disease (COPD) patients with frequent or infrequent exacerbations.
 Methods: Clinical characteristics of eighty COPD patients with chronic bronchitis (CB), emphysema (EM) or asthma-COPD overlap (ACO) phenotypes suffered from acute exacerbation were analyzed. The expressions of CCL3 and CD163 in sputum macrophages were detected by flow cytometry. The expressions of HIF-1α and Cav-1 in sputum macrophages were detected by quantitative PCR (qPCR).
 Results: The age, forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), sputum bacteria positive rate, COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) score between the patients with FE and iFE were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from patients with FE was significantly lower (P<0.01), while CD163 was significantly increased (P<0.01). Meanwhile, HIF-1α and Cav-1 mRNA levels were also significantly increased (P<0.01). The age, sputum bacteria positive rate, CAT score, and mMRC score between the patients of FE and iFE with CB phenotype were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from FE patients was slightly decreased (P<0.05), while CD163 was significantly raised (P<0.01). Meanwhile, HIF-1α and Cav-1 mRNA levels were also significantly increased (P<0.01). The age, duration of disease, FEV1/FVC, sputum bacteria positive rate, CAT score, and mMRC score between the patients of FE and iFE with EM phenotype were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from FE patients was slightly decreased (P>0.05), while CD163 was slightly raised (P>0.05). Meanwhile, HIF-1α levels were slightly elevated (P>0.05), while Cav-1 expression was significantly increased (P<0.01). There were no significant differences in all clinical features between FE and iFE patients with ACO phenotype. The fluorescence intensity of CCL3 in sputum macrophages from patients with FE was significantly lower than that in iFE patients (P<0.01); there was no significant difference in CD163 (P>0.05). At the same time, the expression of HIF-1α (P<0.01) and Cav-1(P<0.05) also increased significantly. There was a significant negative correlation between CCL3 and HIF-1α or Cav-1 in all FE and FE patients with CB phenotype. CD163 was only positively correlated with HIF-1α in those patients and FE patients with EM phenotype. There was a significant negative correlation between CCL3 and HIF-1α in FE patients with ACO phenotype, while CD163 was significantly positively correlated with HIF-1α.
 Conclusion: The clinical features of FE or iFE patients with CB, EM or ACO phenotype are different, and M2 in induced sputum from FE patients are dominant. HIF-1α may play a key role in the polarization process.
Disease Progression ; Forced Expiratory Volume ; Humans ; Lung ; Macrophages ; Phenotype ; Pulmonary Disease, Chronic Obstructive ; Sputum ; Vital Capacity

To investigate the effects of airway epithelial cells on macrophages chemotaxis and inflammatory cytokine expression under hypoxic conditions.
 Methods: Human bronchial epithelial cells (HBE) treated with different concentrations (0, 100, 200, 400, 800 μmol/L) of CoCl2 or transfected with HIF-1α siRNA were co-cultured with THP-1-derived M1 macrophages or M2 macrophages. The chemotactic effects on macrophages were analyzed by Transwell assay. The levels of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were detected by ELISA, and HIF-1α or Cav-1 mRNA expression in HBE or macrophages was detected by RT-qPCR.
 Results: HBE cells promoted macrophages chemotaxis in a time- and concentration-dependent manner. Compared to un-transfected group, the chemotactic ability of HBE transfected with HIF-1α siRNA was significantly weakened (P<0.01). Under the same culture conditions, the chemotaxis of M2 macrophages was greater than that in THP1-derived M1 macrophages. The concentrations of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were increased in a time-and concentration-dependent manner. The concentrations of TNF-α and IFN-γ were increased further after co-culturing for 8 and 12 h; while IL-4, IL-13 and IL-10 concentrations were increased further during 24 h of co-culture. The levels of cytokines in the supernatants of macrophages co-cultured with HBE and transfected with HIF-1α siRNA were significantly lower than those in un-transfected cells (P<0.05 or P<0.01). The reduction of TNF-α or IFN-γ was more obvious. The expression of HIF-1α or Cav-1 mRNA in HBE or macrophages was increased in a concentration-dependent manner after 8 or 12 h co-culture, which was significantly reduced when HBE was transfected with HIF-1α siRNA.
 Conclusion: Airway epithelial cells can enhance macrophages chemotaxis and pro-inflammatory cytokines expressions under hypoxic condition. HIF-1α and Cav-1 may be the important mediators in these processes.
Cell Hypoxia ; Chemotaxis ; Cytokines ; Epithelial Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Macrophages