Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95％reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.

Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95％reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.

The objective of this study was to observe the effect of Astragalus membranaceus on high sugar-induced Caenorhabditis elegans, and to explore its mechanism of action. UPLC-MS method was used to identify the components of Astragalus membranaceus. A high glucose model was established by using Caenorhabditis elegans as a model organism, and the effects of Astragalus membranaceus on body length, body bending, swallowing frequency, and reactive oxygen species (ROS) of the nematode were determined; the effects of Astragalus membranaceus on the expression of mRNA of genes related to the protein skinhead-1 (SKN-1) signaling pathway were examined by using the real-time fluorescence quantitative polymerase chain reaction (PCR). The results showed that compared with the normal group, the nematode body length, body bending, and swallowing frequency expression were significantly reduced and the ROS content in the body was significantly increased in the high glucose state; after the administration of Astragalus membranaceus, the body length, body bending, and swallowing frequency expression were significantly increased, and the ROS content was significantly reduced (P < 0.01). Compared with the normal group, SKN-1, superoxide dismutas-3 (SOD-3), glutathione S-transferase 4 (GST-4), and glutathione S-transferase 7 (GST-7) expression were significantly decreased in Caenorhabditis elegans in the high glucose condition; SKN-1, SOD-3, GST-4, and GST-7 expression were significantly increased after administration of Astragalus membranaceus (P < 0.01). In the present study, we demonstrated that Astragalus membranaceus has an effect on high glucose-induced Caenorhabditis elegans nematodes, and its mechanism of action may be through the modulation of the SKN-1 signaling pathwaym in order to ameliorate the oxidative stress response induced by high glucose.

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Objective:To evaluate the value of ultrasonography in evaluating the influential factors of early insufficient flow after central venous catheter placement in dialysis patients.Methods:Three hundred and twenty seven hemodialysis patients who underwent central venous catheterization at the Affiliated Hospital of Chengde Medical College from May 2016 to June 2019 were selected. According to the catheter flow, the patients were divided into the low catheter flow group(43 cases) and the normal catheter flow group(284 cases). The distribution variance of clinical features(age, gender, blood pressure) were compared and whether some ultrasonic parameters(position of catheter tip, left ventricular ejection fraction, left atrial end-systolic diameter, left ventricular end-diastolic diameter, distance from the catheter tip to superior vena cava beyond right atrial opening) had influence on the insufficient catheter flow in the early stage between the two groups were analyzed.Results:The differences of left ventricular ejection fraction, left atrial end-systolic diameter and position of catheter tip between the two groups were statistically different( P<0.05). However, univariate and multivariate analyses showed that there were significant differences in catheter tip approaches and touches the wall of right atrium( OR=5.393, 95% CI=2.039-14.263, P=0.001), increased left atrial end-systolic diameter( OR=0.321, 95% CI=0.124-0.827, P=0.019), left ventricular ejection fraction in critical range( OR=2.953, 95% CI=1.113-7.835, P=0.030) and decreased left ventricular ejection fraction( OR=5.828, 95% CI=1.869-18.174, P=0.002) were the independent risk factors of early insufficient catheter flow. Conclusions:Insufficient catheter flow after central venous catheterization is related to catheter position, left atrial end-systolic diameter and left ventricular ejection fraction. Ultrasonography evaluation is a primary method to observe the position of the catheter tip in dialysis patients and diagnose the early insufficient catheter flow after central venous catheterization.

Hemorrhagic shock refers to the pathophysiological process of reduced effective circulating blood volume,insufficient tissue perfusion,disorder of cell metabolism,and impaired organ function caused by the body's massive blood loss due to various causes.The key to improving the success rate of its treatment is to recover effective tissue perfusion as soon as possible to improve the oxygen supply to tissue cells,rebalance oxygen supply and demand,and restore normal cell functions while eliminating the cause of shock.The key to emergent care of hemorrhagic shock is timely and effective fluid resuscitation,which can directly affect the prognosis of patients.How to effectively provide fluid resuscitation is a clinical challenge that doctors must take into consideration.Direct peritoneal resuscitation represents a new approach by which the required infusion fluid is administered into the peritoneal cavity by means of abdominocentesis and absorbed through the peritoneal blood vessels and lymphatic vessels.This fluid resuscitation technique is characterized by fixed puncture points and easy operations,and it is less affected by environmental factors.Using this technique,the fluid can be infused at once in a short time.When it is difficult to establish an intravenous infusion pathway,a fluid resuscitation pathway can be quickly established,which can effectively improve hemodynamic indicators and achieve fluid resuscitation against shock.In addition,at the same time of intravenous fluid resuscitation,direct peritoneal resuscitation can improve the effect of intravenous resuscitation,which is of great significance in improving micro-circulation,increasing organ blood flow,reducing organ and tissue edema,and inhibiting systemic inflammation.This article attempts to review the merits,fluid selection and mechanism of direct peritoneal resuscitation,aiming to provide new ideas for fluid resuscitation of hemorrhagic shock.

BACKGROUND: Heterotopic ossification (HO) is a known complication of hip arthroscopy. We investigated incidence of HO after hip arthroscopy and determined whether revision for HO improved outcome. METHODS: A retrospective study was conducted on 242 patients (140 men and 102 women, mean age: 36.2 ± 9.5 years) who underwent hip arthroscopy for femoroacetabular impingement (FAI) between January 2016 and January 2018. The average follow-up period was 22.88 ± 11.74 months (range: 11-34 months). Thirteen (5.37%) cases of HO (six men and seven women, five left hips and eight right hips; mean age: 37.5 ± 4.7 years) were observed. Among them, four cases with HO with obvious pain symptoms and persistent non-remission underwent revision surgery to remove HO. Monthly follow-up was conducted. Visual analog scale (VAS), modified Harris Hip Score (mHHS), and non-Arthritis Hip Score (NAHS) were evaluated and compared between HO and non-HO patients. Independent sample t test, Mann-Whitney U test and the Chi-square test were used for inter-group comparisons. HO degree was evaluated using Brooker classification. Symptoms and function were evaluated before and after revision. RESULTS: A total of 242 patients were involved in this study. Thirteen cases (5.4%) had imaging evidence of HO. Nine (9/13) were classified as Brooker stage I, three (3/13) Brooker stage II, and one (1/13) Brooker stage III. HO was detected by ultrasonography as early as 3 weeks after operation. After primary surgery, the mHHS of the HO group and non-HO group increased by 13.00 (8.50, 25.50) and 24.00 (14.00, 34.50) points (Z = -1.80, P = 0.08), NAHS increased by 18.00 (9.50, 31.50) and 26.00 (13.50, 36.00) points (Z = -1.34, P = 0.18), and VAS decreased by 3.00 (2.00, 4.00) and 4.00 (3.00, 4.50) points (Z = -1.55, P = 0.12). Average follow-up time after revision was 9.00 ± 2.94 months; mHHS increased by 34.75 points (t = -55.23, P < 0.01) and NAHS by 28.75 points (t = -6.03, P < 0.01), and VAS decreased by 4 points (t = 9.80, P < 0.01). HO and non-HO patients were similar for demographic and surgical data, and clinical and functional scores. CONCLUSION HO incidence after arthroscopic treatment of FAI is similar to that found in previous studies. Most HO have no effect on clinical symptoms. Patients who undergo revision HO resection show improvement in pain and joint function.
Adult ; Arthroscopy ; adverse effects ; Female ; Femoracetabular Impingement ; surgery ; Hip Joint ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Ossification, Heterotopic ; diagnosis ; etiology ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the pathogen composition and clinical features of preterm infants with sepsis, and to provide a basis for early identification and treatment of sepsis in preterm infants. METHODS: A retrospective analysis was performed for the clinical data of 371 preterm infants with sepsis who had a positive blood culture between January 2014 and May 2018. According to the time of onset, the preterm infants were divided into an early-onset group (an age of onset of <7 days) with 73 preterm infants and a late-onset group (an age of onset of ≥7 days) with 298 preterm infants. The two groups were compared in terms of pathogen composition and clinical features (initial symptoms, laboratory examination results at the time of onset, comorbidities, and prognosis). RESULTS: There was a higher proportion of infants with Klebsiella pneumoniae infection in the late-onset group (P<0.05), while there was a higher proportion of infants with Escherichia coli, Streptococcus agalactiae or Listeria infection in the early-onset group (P<0.05). The early-onset group had a significantly higher proportion of infants with dyspnea than the late-onset group (P<0.05). Compared with the late-onset group, the early-onset group had significantly shorter time to negative conversion of blood culture, duration of antibiotic use before infection, and indwelling time of deep venous catheterization (P<0.05), and the late-onset group had a significantly higher incidence rate of neonatal necrotizing enterocolitis than the early-onset group (P<0.05). The early-onset group had a significantly higher rate of treatment withdrawal than the late-onset group (P<0.05). CONCLUSIONS Preterm infants with sepsis lack typical clinical manifestations and laboratory examination results at the time of onset. There are certain differences in pathogen composition and clinical features between preterm infants with early- and late-onset sepsis. Possible pathogens for sepsis should be considered based on age in days at the time of onset and related clinical features.
Enterocolitis, Necrotizing ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Retrospective Studies ; Sepsis ; Streptococcus agalactiae