This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Objective:To investigate the association between ureaplasma urealyticum (UU) colonization in the respiratory tract and bronchopulmonary dysplasia (BPD) in extremely preterm or extremely low birth weight infants.Methods:This was a retrospective study involving preterm infants with gestational age <28 weeks or birth weight <1 000 g who was hospitalized in the Neonatal Intensive Care Unit (NICU) of Chengdu Women's and Children's Central Hospital from June 2019 to March 2022. Respiratory tract secretion was collected for UU DNA detection within 24 h after admission. All the participants were divided into the UU-positive or negative groups based on the detection results. Clinical characteristics of the two groups were analyzed using Mann-Whitney U, t-, or Chi-square tests (Fisher exact test). Results:A total of 82 infants were enrolled, including 31 cases (37.8%) in the UU-positive group and 51 patients (62.2%) in the negative group. Among the 30 cases treated with azithromycin in the positive group, 27 (90.0%, 27/30) turned negative after two courses of treatment. The rates of premature rupture of membranes [51.6% (16/31) vs 17.6% (9/51), χ2=10.50] and prenatal antibiotic exposure [71.0% (22/31) vs 47.1% (24/51), χ2=4.47] in the UU-positive group were both higher than those in the UU-negative group (both P<0.05). Multivariate logistic regression analysis showed that premature rupture of membranes ( OR=5.893, 95% CI: 2.016-17.228) and gestational age ( OR=0.663, 95% CI: 0.441-0.999) were independent risk factors for UU colonization (both P<0.05). UU-positive group had a longer duration of oxygen use [ M ( P25- P75), 1 756 h (1 385-2 088 h) vs 1 357 h (1 128-1 656 h), Z=2.98], a longer length of hospital stay [81 d (70-105 d) vs 68 d (59-84 d), Z=3.05], and higher hospitalization costs [(201 574±70 326) yuan vs (161 288±53 412) yuan, t=－2.74] compared to the UU negative group (all P<0.05). The incidence of BPD [74.2% (23/31) vs 47.1% (24/51), χ2=5.80] and retinopathy of prematurity [93.4% (29/31) vs 74.5% (38/51), χ2=4.68] in the UU positive group was higher than those in the UU-negative group (both P<0.05). No significant correlation was found between UU colonization and the severity of BPD ( P>0.05). Conclusion:UU colonization may increase the incidence of BPD, but there was no clear correlation with the severity of BPD.

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.
Humans ; Female ; Lymphatic Metastasis ; B7-H1 Antigen/metabolism* ; Triple Negative Breast Neoplasms/pathology* ; Breast Neoplasms ; Osteonectin/therapeutic use* ; Prognosis

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.
Humans ; Female ; Lymphatic Metastasis ; B7-H1 Antigen/metabolism* ; Triple Negative Breast Neoplasms/pathology* ; Breast Neoplasms ; Osteonectin/therapeutic use* ; Prognosis

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective:To investigate the frequency of myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) in peripheral blood of patients with systemic lupus erythematosus (SLE) and their relationship with renal injury.Methods:The frequency of peripheral mDC and pDC in 102 SLE patients and 10 healthy controls were detected by flow cytometry. The quantitative data were expressed by [ M( P25, P75)]. The measurement data of the two groups with non-normal distribution was analyzed by Mann Whitney U test. The correlation between the two groups was analyzed by Spearman rank correlation analysis and multiple linear regression. Results:The frequency of pDC [14.00%(7.92%, 19.65%) vs 24.55%(19.68%, 32.90%), Z=-3.163, P<0.01] and mDC [21.25%(13.28%, 32.83%) vs 34.85%(24.58%, 41.93%), Z=-2.607, P<0.01] in the peripheral blood of 102 patients with SLE were significantly lower than those of healthy controls. The frequency of pDC [9.09%(7.31%, 17.38%) vs 24.55%(19.68%, 32.90%), Z=-3.033, P=<0.01] and mDC [9.40%(7.88%, 21.60%) vs 34.85%(24.58%, 41.93%), Z=-3.231, P<0.01] in 12 patients with newly diagnosed SLE were also significantly lower than those in healthy controls. After adjustedfor confounding factors, multivariate analysis showed that SLEDAI level was the main factor influencing the frequency of pDC ( P=0.019) and mDC ( P<0.01). In addition, pDC[8.02%(2.25%, 9.97%) vs 16.70%(11.80%, 24.60%), Z=-2.490, P=0.015] and mDC[8.80%(5.99%, 12.80%) vs 20.20%(11.20%, 42.80%), Z=-2.226, P=0.029] in patients with active LN were also significantly lower than that of patients with stable LN. The mDC frequency was positively correlated with the levels of complement C3 ( r=0.455, P<0.01) and C4 ( r= 0.289, P, P<0.01). Conclusion:The frequency of mDC and pDC in SLE patients is significantly abnormal, which is closely related to disease activity. In addition, pDC and mDC may be involved in the occurrence and development of LN.