Objective:To explore the heterogeneity among keloids before and after radiotherapy and identify the changes of key cell subpopulations and their interactions utilizing single cell RNA sequencing technology.Methods:Four patients provided a total of 12 samples, each consisting of keloid tissue before and after radiotherapy and the normal skin tissue adjacent to the untreated keloid. The keloid was divided into left and right sides from the midline, and the left-side keloid was fractionally irradiated with 20 Gy electron beam in total in 4 consecutive days. The right-side keloid was irradiated with 10 Gy in 2 fractions before surgery and 10 Gy in 2 fractions after surgery.Results:A total of 25 573 fibroblasts were analyzed and categorized into nine subgroups (fibroblasts 1-9). The proportion of fibroblast-2 increased after radiotherapy ( t=4.70, P<0.05). The number of classical monocytes and macrophages increased after radiotherapy, but there was no significant difference due to the shorter time of sample taking at 2 d after radiotherapy ( P>0.05). Macrophages (4 723 cells) were further divided into four categories. CellPhoneDB analysis showed that type-3 macrophages interacted significantly more closely with fibroblasts than type-1 and type-2 macrophages. The most prominent signaling pathways for the interactions between type-3 macrophages and major fibroblast subtypes were the collagen signaling pathway and the chemerin signaling pathway. These interactions were more pronounced in the keloid samples after radiotherapy. Conclusions:The interactions between type-3 macrophages and fibroblasts (such as fibroblast-2) may serve as an important point for future studies on radio-sensitization of keloids.

BACKGROUND: Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States. METHODS: This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes. RESULTS: After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P  < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P  = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses. CONCLUSIONS Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.
Adult ; Humans ; United States/epidemiology* ; Nitrates/adverse effects* ; Nutrition Surveys ; Thiocyanates/urine* ; Perchlorates/urine* ; Creatinine ; Environmental Exposure ; Renal Insufficiency, Chronic/epidemiology* ; Logistic Models

Objective:To explore the speech features of female patients with anhedonic depression and their recognition of pleasure deficient symptoms.Methods:A total of 102 female depression patients who were hospitalized at Nanjing Brain Hospital from September 2020 to October 2021 were selected, including 62 anhedonic depression patients (anhedonic group) and 40 non-anhedonic depression patients (non-anhedonic group). A total of 50 female healthy controls were recruited during the same period.All participants were evaluated by the 17-item Hamilton depression scale (HAMD-17), Snaith-Hamilton pleasure scale (SHAPS), and the temporal experience of pleasure scale (TEPS), as well as voice acquisition.SPSS 23.0 software was used for data processing.Statistical analysis was conducted using one-way ANOVA, non-parametric tests, Logistic regression, and receiver operating characteristic curve.Results:Compared with the non-anhedonic group, the anhedonic group showed significant changes in 15 voice features(all P<0.05), including Mel-frequency cepstral coefficients, formant frequencies, intensity, and energy features.Among these features, Mel-frequency cepstral coefficients exhibited the highest accuracy in identifying anhedonic depression, with sensitivity of 47.5%, specificity of 91.9%, area under curve (AUC) of 0.751, 95% CI=0.686-0.866.Formant frequencies could identify female anhedonic depression, with a sensitivity of 90.0%, a specificity of 40.3%, an AUC of 0.647, and 95% CI=0.605-0.824.Energy features could identify anhedonic deficient depression, with a sensitivity of 60.0%, a specificity of 74.2%, an AUC of 0.679, and 95% CI=0.587-0.804.Intensity features could identify female anhedonic depression, with a sensitivity of 70.0%, a specificity of 58.1%, an AUC of 0.640, and 95% CI=0.554-0.769. Conclusion:Mel-frequency cepstral coefficients, formant frequencies, intensity features, and energy features may have specific changes in female patients with anhedonic depression.The Mel-frequency cepstral coefficients has the highest recognition accuracy for anhedonic symptoms in female depression patients, and is expected to become an objective evaluation index for female anhedonic depression.

Objective To exploring the mechanism of Jinshui Chenfei formula(JCF)in ameliorating silica(SiO2)-induced silicosis fibrosis based on endogenous metabolite changes.Methods A total of 32 SPF male Sprague-Dawley(SD)rats were divided into normal control group,model group,JCF group(9.72 g·kg-1·d-1),and Tetrandrine group(27 mg·kg-1·d-1)according to random number table method.The experimental silicosis model was established by intratracheal injection with SiO2 suspension(250 mg/kg)on day 1.From week 5-8,silicosis rats were treated with tetrandrine or JCF.On the end of week 8,the changes of pulmonary function index,including forced vital capacity(FVC),tidal volume(TV)and lung dynamic compliance(Cydn)were detected.The pathological changes of lung tissue were analyzed by hematoxyline-osin(HE)staining and Masson staining,the severity of focal alveolitis and fibrosis was also evaluated using the Szapiel scale and the Ashcroft scale,the positive staining of collagen Ⅰ(COL Ⅰ)and COL Ⅲ was detected using immunohistochemistry;the protein expression of transforming growth factor-β1(TGF-β1),fibronectin(FN),andα-smooth muscle actin(α-SMA)were measured by Western blotting.The rat serum samples were further screened for differential metabolites using ultra performance liquid chromatographytandem quadrupole time of flight mass spectrometr(UPLC-Q-TOF-MS)and pathway analysis was performed based on MetaboAnalyst 5.0.Results Compared with those in the normal control group,pathological changes such as alveolar structure destruction,the fibrous nodules encapsulated SiO2 particles were increased in lung tissues of rats in model group,alveolitis score and pulmonary fibrosis score were significantly higher(alveolitis score:2.62±0.27 vs.0.20±0.15,pulmonary fibrosis score:5.42±0.66 vs.0.50±0.84,both P<0.01);pulmonary function index including Cydn,FVC,and TV were significantly decreased[Cdyn(mL/cmH2O):0.26±0.03 vs.0.33±0.03,FVC(mL):8.09±0.47 vs.10.99±0.38,TV(mL):1.95±0.19 vs.2.53±0.26,all P<0.01];positive staining of COL Ⅰ,COL Ⅲ and ɑ-SMA,FN,TGF-β1 proteins expression showed higher in lung tissues[positive staining of COL Ⅰ(A value):13.47±1.76 vs.5.77±0.45;positive staining of COL Ⅲ(A value):10.39±0.47 vs.6.19±0.77,FN protein expression(FN/GAPDH):0.33±0.02 vs.0.21±0.07,α-SMA protein expression(α-SMA/GAPDH):1.78±0.16 vs.1.11±0.24,TGF-β1 protein expression(TGF-β1/GAPDH):0.52±0.10 vs.0.11±0.46,all P<0.01].Compared with the model group,the pathological changes of lung tissues were almost restored,alveolitis score and lung fibrosis score were significantly reduced in JCF and Tetrandrine groups(alveolitis score:1.10±0.15,1.33±0.31 vs.2.62±0.27,pulmonary fibrosis score:3.50±0.45,4.33±0.98 vs.5.42±0.66,all P<0.01);the pulmonary function index Cydn,FVC and TV were significantly increased[Cdyn(mL/cmH2O):0.32±0.05,0.31±0.04 vs.0.26±0.03,FVC(mL):9.41±0.85,8.70±0.92 vs.8.09±0.47,TV(mL):2.70±0.19,2.27±0.15 vs.1.95±0.19,all P<0.05];positive staining of COL Ⅰ,COL Ⅲ,and protein expression of FN,ɑ-SMA,and TGF-β1 in lung tissues was significantly decreased[COL Ⅰ(A value):7.09±0.67,8.13±0.64 vs.13.47±1.76,COL Ⅲ(A value):8.19±0.66,8.52±0.22 vs.10.39±0.47,FN protein expression(FN/GAPDH):0.19±0.06,0.24±0.03 vs.0.33±0.02,α-SMA protein expression(α-SMA/GAPDH):0.89±0.41,0.88±0.08 vs.1.78±0.16,TGF-β1 protein expression(TGF-β1/GAPDH):0.04±0.03,0.06±0.01 vs.0.52±0.10,all P<0.05].Metabolomics analysis showed that a total of 10 major differential metabolites were identified between normal control group,model group and JCF group,including arachidonic acid,palmitic acid,indole-3-acetic acid,propionylcarnitine,(S)-4-hydroxymandelonitrile,nalidixic acid,benzocaine,gramine,4-ethylphenol,N-benzylfor mamide.The differential metabolites in silicosis rats reversed by JCF treatment were mainly enriched,including unsaturated fatty acid biosynthesis,arachidonic acid metabolism,tryptophan metabolism,fatty acid elongation,fatty acid degradation and biosynthesis.Conclusion JCF could effectively improve the silicosis fibrosis,which is mainly related to biosynthesis of unsaturated fatty acids biosynthesis,arachidonic acid metabolism,tryptophan metabolism,fatty acid elongation,fatty acid degradation and biosynthesis.

AIM:To investigate the effect of Tongsai granules(TSG)on epithelial barrier dysfunction in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and the underlying mechanism.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into control group,model group,TSG group,and moxifloxacin(MXF)+salbutamol(STL)group.Rat COPD model was established over 8 weeks.On day 3 of week 9,the rats with COPD were intratracheally administered Klebsiella pneumoniae to establish the AECOPD model.On days 1 to 2 and 4 to 7 in week 9,saline was administered via oral gavage to the rats in control and model groups,and the rats in TSG and MXF+ STL groups were treated daily with TSG and MXF+STL by gavage,respectively.Peak expiratory flow(PEF),histopatho-logical changes,and the expression levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),matrix me-talloproteinase 2(MMP2),MMP9,zonula occludens-1(ZO-1),E-cadherin(E-Cad)and occludin(OCC)were deter-mined.Moreover,human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract(CSE)and treated with different TSG fractions,and the protein levels of ZO-1,E-Cad,OCC,epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)were determined.RESULTS:Treatment with TSG significantly reduced bronchial wall thickness,mean linear intercept,and the levels of IL-1β,IL-6,TNF-α,MMP2 and MMP9(P＜0.05 or P＜0.01),significantly increased mean alveolar number and PEF(P＜0.01),and up-regulated the ZO-1,E-Cad and OCC protein levels(P＜0.01)in the lungs of AECOPD rats.Treatment with TSG2,the second TSG fraction,increased the protein levels of ZO-1,E-Cad and OCC in a dose-dependent manner in CSE-exposed BEAS-2B cells(P＜0.05 or P＜0.01).Network pharmacology analysis of 328 targets of the com-pounds in TSG2 and 3 864 genes related to AECOPD suggested that TSG2 relieved AECOPD likely through the regulation of ERBB2,ERK,EGFR,IL and WNT signaling pathways.Treatment with TSG2 also inhibited CSE-induced increases in p-EGFR and p-ERK levels in BEAS-2B cells(P＜0.05 or P＜0.01).CONCLUSION:Treatment with TSG could maintain airway epithelial barrier function in AECOPD rats,likely through the inhibition of EGFR/ERK signaling pathway.

Objective:To analyze the influencing factors for depression in primary school children aged 9-10 years in Jiangsu Province, and to construct a risk prediction model.Methods:A retrospective study.A total of 1 162 primary school children aged 9-10 years from 3 primary schools in 3 regions of Jiangsu Province were recruited.Their demographic data were collected, and they were surveyed by the Depression Anxiety Stress Scales-21 (DASS-21), the Strengths and Difficulties Questionnaire (SDQ), and the Family Environment Scale (FES). Children were divided into control group (1 059 cases) and depression group (103 cases) based on the depression scores obtained from the DASS-21 scale.Multivariate Logistic regression analysis was used to analyze the influencing factors for depression in primary school students aged 9-10 and construct a risk prediction model. Results:There were significant differences in the economic development region, physical activities, academic performance, student cadres, parents′ education level, frequency of parental quarrels, SDQ and FES dimension scores between control group and depression group (all P<0.05). Among them, economic development areas (Northern Jiangsu and Southern Jiangsu), student cadres, father′s education level (elementary school and below) and intimacy of the FES scale were protective factors for depression in elementary school children; while emotional symptoms, peer problems and the total difficulty score in the SDQ scale, and the conflict in the FES scale were the risk factors for depression in elementary school children.The prediction model was created based on the influencing factors: Logit ( P)=-1.390×economic development area (Northern Jiangsu) -1.508×economic development area (Southern Jiangsu) -1.248×student cadres -2.206×father′s education level (primary school and below) -1.145×father′s education level (junior high school)+ 3.316×emotional symptoms in the SDQ+ 0.979×peer problems in the SDQ+ 2.520×total difficulty score in the SDQ -1.697×cohesion in the FES + 0.760×conflict in the FES -0.678.The area under the curve of receiver operating characteristic was 0.931, with the sensitivity and specificity of 85.42% and 91.83%, respectively. Conclusions:The regional level of economic development, class or school cadres, father′s education level, peer problems, total difficulty score, cohesion and conflict in the family are influencing factors for depression among primary school children aged 9-10 years in Jiangsu Province.The created prediction model can effectively assess the depressive risk factors in this population, which is conductive to achieve the early recognition and intervention of depression in them.

Objective:To improve the understanding of autoimmune lymphoproliferative syndrome (ALPS).Methods:The clinical data of the proband and his family members in Children's Hospital Affiliated to Zhengzhou University in August 2018 were retrospectively analyzed, and the peripheral blood DNA of the proband, his parents and siblings was extracted. High-throughput next-generation sequencing was used to make gene analysis and validation. Phenotype and genotype of them were also analyzed. Relevant literature was reviewed.Results:The proband was a 1-year and 1-month old boy with hemolytic anemia, thrombocytopenia and splenomegaly as the main manifestations. The double negative T cells and the Vitamin B 12 of the proband were significantly increased and the autoantibodies were positive. The boy's father had a history of splenomegaly. His elder brother and sister had similar clinical manifestations. The results of next-generation sequencing showed that the FAS gene frameshift mutation (c.648delT) was detected in this boy and his father, elder brother and sister, which was a new mutation. After immunosuppressive treatment, the symptoms of the boy improved and the blood cells increased. Conclusions:The frameshift mutation of FAS gene may be the cause of the disease in this ALPS pedigree. Clinically, it is necessary to consider ALPS for children with unexplained hemocytopenia and hepatosplenomegaly. Double-negative T cells, autoantibodies, Vitamin B 12 should be tested, and high-throughput gene sequencing should be performed if necessary.

Objective:To investigate the clinical characteristics and gene mutations of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) secondary to familial hemophagocytic syndrome (FHL).Methods:The clinical features, disease evolution, gene mutation and genetic characteristics of 1 SPTCL patient secondary to FHL in Henan Children's Hospital in June 2012 were analyzed retrospectively, and the related literatures were reviewed.Results:The UNC13D of FHL patient was homozygous mutation accompanied by STXBP2 heterozygous mutation, while that of his parents and elder brother was heterozygous mutation. After regular chemotherapy with HLH-2004 regimen, the disease relapsed 4 years later, and secondary SPTCL developed after 1 year of remission with the second chemotherapy. After giving SMILE regimen chemotherapy, allogeneic hematopoietic stem cell transplantation was performed, and now the patient had disease-free survival.Conclusions:The detection of related genes in children with hemophagocytic syndrome should be improved in time to confirm the diagnosis of primary disease. FHL can follow SPTCL, and chemotherapy combined with allogeneic hematopoietic stem cell transplantation can be the only method to cure this disease.

Objective:To investigate the diagnosis and treatment of congenital leukemia and the main factors affecting its prognosis.Methods:Clinical data of children with congenital leukemia admitted to Zhengzhou Children′s Hospital from July 2007 to December 2017 were retrospectively collected.Their clinical characteristics, chemotherapy and factors affecting their long-term survival were analyzed.Results:A total of 23 cases of congenital leukemia were collected, who mostly complained of " increased white blood cells, skin nodules and skin hemorrhage" . Among them, 10 cases abandoned the treatment, who all died according to the follow-up results.Among the 13 treated cases, 7 cases were male, and 6 were female.One of the 13 cases was a twin.Eight cases were acute myeloid leukemia, and 5 cases were acute lymphoblastic leukemia.One case did not perform the fusion gene test. MLL gene was positive in 2 cases and negative in 10 cases.No other fusion genes were detected.Karyotype analysis showed that 1 case was 21-trisomy and 12 cases had a normal karyotype.All 13 patients received symptomatic and/or reduced chemotherapy.The median follow-up time was 4 years and 11 months.Six cases recovered and 7 cases died during the follow-up.One case was diagnosed with acute lymphoblastic leukemia on the 6 th day after the birth in another hospital.He was not treated timely and came to Zhengzhou Children′s Hospital with general contract blocks at the age of 32 days.After checking, he was diagnosed with center leukemia and testicular leukemia.He developed a severe infection in the lung and brain after strong chemotherapy, and died even after the remote consultation with Lurie Children′s Hospital of Chicago.The other 6 cases died of severe infection and multiple organ injuries after chemotherapy, and no one died of leukemia relapse. Conclusion:Reduction chemotherapy may be an important treatment to children with congenital leukemia.

ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia. However, the neural mechanisms underlying this association are unknown. Given that ZNF804A upregulates the expression of COMT, we hypothesized that ZNF804A may influence brain activity by interacting with COMT. Here, we genotyped ZNF804A rs1344706 and COMT rs4680 in 218 healthy Chinese participants. Amplitudes of low-frequency fluctuations (ALFFs) were applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680. The ALFFs of the bilateral dorsolateral prefrontal cortex showed a significant ZNF804A rs1344706 × COMT rs4680 interaction, manifesting as a U-shaped modulation, presumably by dopamine signaling. Significant main effects were also found. These findings suggest that ZNF804A affects the resting-state functional activation by interacting with COMT, and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia.