[Retrospective study on the diagnosis, treatment, and follow-up of 85 cases of hypophosphatemic rickets in children]. / 85ä¾‹ä½Žè¡€ç£·æ€§ä½å»ç— æ‚£å„¿è¯Šæ–­ã€æ²»ç–—ä¸Žéšè®¿çš„å›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To study the diagnosis, treatment, and complications of hypophosphatemic rickets (HR) in children, explore effectiveness evaluation indicators for the disease, and understand the pattern in height growth among these patients. METHODS: A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022. RESULTS: Among the 85 children with HR, there were 46 males (54%) and 39 females (46%). The age at initial diagnosis ranged from 6 months to 13 years and 9 months, with a median age of 2.75 years. The average height standard deviation score was -2.0±1.1. At initial diagnosis, children exhibited reduced blood phosphate levels and elevated alkaline phosphatase (ALP), with 99% (84/85) presenting with lower limb deformities. The positive rate for PHEX gene mutations was 93% (55/59). One year post-treatment, there was a significant reduction in ALP levels and the gap between the lower limbs (P<0.05). The fastest height growth occurred in the first year after treatment, at 8.23 cm/year, with a peak height velocity (PHV) phase lasting about two years during puberty. The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children. Major complications included nephrocalcinosis and hyperparathyroidism. The incidence rate of nephrocalcinosis in the first year after treatment was 55% (22/40), which increased with the duration of the disease (P<0.001); an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis (OR=1.740, P<0.001). The incidence of hyperparathyroidism in the first year after treatment was 64% (27/42). CONCLUSIONS: For children presenting with lower limb deformities, short stature, and slow growth, early testing for blood levels of phosphate, calcium, and ALP, along with imaging examinations of the lower limbs, can aid in the early diagnosis of HR. Genetic testing may be utilized for definitive confirmation when necessary. ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR. Compared to normal children, children with HR demonstrate a lower height increase during the PHV phase, necessitating close follow-up and timely adjustment of treatment plans Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 677-682.

[Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children]. / è¡€æ¸ æˆçº¤ç»´ç»†èƒžç”Ÿé•¿å› å­23å¯¹å„¿ç«¥ä½Žè¡€ç£·æ€§ä½å»ç— çš„è¯Šæ–­ä»·å€¼ç ”ç©¶.

OBJECTIVES: To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children. METHODS: A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed. RESULTS: The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05). CONCLUSIONS: Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

Long-term follow-up of self-expandable metallic stents in benign tracheobronchial stenosis: a retrospective study.

BACKGROUND: Self-expandable metallic stents (SEMSs) have enabled a approving management of malignant airway stenosis. However, the long-term efficacy and safety of this treatment in patients with benign airway stricture are unclear. We conducted this study to retrospectively determine the efficacy and long-term outcomes in patients who have undergone SEMS placement for benign tracheobronchial stenosis. METHODS: All patients treated with SEMSs from July 2003 to June 2016 were reviewed for symptomatic response, complications, and long-term outcomes. RESULTS: Total 131 stents were successfully deployed in 116 patients. Ninety-eight patients demonstrated clinical improvement after stent insertion (84.48%; 95% confidence interval [CI]: 77.89-91.07). Compared with uncovered stents, covered stents were associated with more sore throats complaints or chest pain (13.89% versus 28.81%, P = 0.036) and with higher incidences of major and minor granulation tissue formation and with recurrent stenosis (4.17% versus 15.25%, P = 0.029; 11.11% versus 37.29%, P < 0.0001 and 9.72% versus 28.81%, P = 0.005, respectively). Each covered and uncovered stent developing tissue hyperplasia required a median of 2 (range: 1-15) and 1(range: 1-7) fibrobronchoscope with electrocautery therapy, respectively. At follow-up (median: 1276 days; range: 2-4263), 68 patients had complete resolution, 15 remained under interventional treatment, 8 had bronchial occlusions, 7 underwent surgery, 14 were lost to follow-up, and 4 died of stent unrelated causes. CONCLUSION: SEMS placement achieved most clinical improvement among patients in our study, if adequate endotracheal measures were used to address stent-related complications. The use of permanent SEMSs for benign tracheobronchial stenosis was effective and safe for the majority of patients in a long-term follow-up. TRIAL REGISTRATION: The study has been retrospectively registered in the China Clinical Trial Registry on October 21, 2018 (Registry ID: ChiCTR1800019024 ).

Three novel mutations of the G6PC gene identified in Chinese patients with glycogen storage disease type Ia.

UNLABELLED: Glycogen storage disease type Ia (GSDIa) is an autosomal recessively inherited disease characterized by poor tolerance to fasting, growth retardation, and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Germline mutations of glucose-6-phosphatase (G6PC) gene have been identified as a cause of GSDIa. In this study, we performed mutation analysis in five Chinese GSDIa patients belonging to five unrelated families by direct DNA sequencing. All patients were clinically classified as GSDIa. Mutation analysis of the G6PC gene revealed that all patients carried biallelic G6PC mutations (p.Ile341Asn, p.Ala274Val, p.Phe80Ile, p.Gly118Asp, p.Arg83His, c.262delG, and c.648G>T). Of the seven different mutations identified, three were found to be novel. All of the novel mutations were missense (p.Ala274Val, p.Phe80Ile, and p.Gly118Asp). The c.262delG mutation which leads to a frame-shift and truncated forms of glucose-6-phosphatase was present in three unrelated patients (one homozygote and two heterozygotes). CONCLUSION: By direct DNA sequencing, three novel G6PC variations were identified which expanded the G6PC mutation spectrum, and provided conclusive genetic evidences for the definitive diagnosis of the Chinese patients.

[The efficacy of intermittent pneumatic compression in the prevention of venous thromboembolism in medical critically ill patients].

OBJECTIVE: To evaluate the efficacy of intermittent pneumatic compression (IPC) in the prevention of venous thromboembolism (VTE) in medical critically ill patients. METHODS: A prospective, randomized, controlled study was conducted. One hundred and sixty-two medical critically ill patients were randomly assigned to IPC group and control group by random number table after admitted to intensive care unit (ICU) from June 2008 to June 2010. Patients under anticoagulation medicine therapy were excluded. Patients in the IPC group were treated with IPC to prevent VTE after ICU admission. No measures were taken to prevent VTE in the control group. The rate of VTE [deep vein thrombosis (DVT) and pulmonary embolism (PE)], duration of mechanical ventilation(MV), the length of stay in ICU, rate of non-sudden cardiac death and ICU mortality rate and related side-effects of IPC were compared during the subsequent 28 days between two groups. RESULTS: Compared with control group, IPC group was shown to have a significantly lower rate of DVT [3.80%(3/79) vs. 19.28%(16/83), P<0.01], lower rate of PE [0 (0/79) vs. 9.64%(8/83), P<0.01] and lower rate of non-sudden cardiac death [1.26%(1/79) vs. 7.23%(6/83), P<0.01]. Compared with control group, duration of MV (days: 8±6 vs. 9±8) and length of stay in ICU (days: 9±7 vs. 10±7) were shorter, and the ICU mortality rate of 28 days (24.05% vs. 31.32%) was lower in the IPC group, but they were not statistically significant (all P>0.05). No related side-effects were found in the IPC group. CONCLUSION: IPC can prevent VTE, and lower the rate of non-sudden cardiac death, and it is safe in medical critically ill patients.

[The effect of breviscapine on the pulmonary arterial pressure and the expression of Rho-kinase in pulmonary arterioles of hypoxic rats].

OBJECTIVE: To observe the effect of breviscapine on the pulmonary artery pressure and the Rho-kinase and Rho-kinase mRNA in pulmonary arterioles of rats treated with hypoxia, and therefore to explore the mechanisms of breviscapine on hypoxic pulmonary hypertension. METHODS: Eighteen adult male SD rats were randomly divided into 3 groups. One group was exposed to air (normal group), the second group was exposed to isobaric hypoxia for 3 weeks (hypoxic group), and the third group was exposed to hypoxia for 3 weeks and treated with breviscapine (preventive group). Cardiac catheterization was used to measure the mean pulmonary arterial pressure (mPAP). The heart was isolated, and the right ventricle (RV), left ventricle plus ventricular septum (LV + S) were weighed to calculate the ratio RV/(LV + S). The ratio of vascular wall thickness/vascular external diameter (WT%) and the ratio of vascular wall area/total vascular area (WA%) were measured by image analysis. The quantity of Rho-kinase and Rho-kinase mRNA in rat pulmonary arterioles were determined by immunohistochemistry and in situ hybridization respectively. RESULTS: The mPAP in the preventive group [(19.83 +/- 1.47) mm Hg, 1 mm Hg = 0.133 kPa] was significantly lower than that of the hypoxic group [(27.3 +/- 5.0) mm Hg], t = 4.28, P < 0.05. The RV/(LV + S) in the preventive group (0.29 +/- 0.03) was significantly lower than that in the hypoxic group (0.34 +/- 0.05, t = 2.39, P < 0.05). The WT% and WA% in the preventive group (25 +/- 5 and 45 +/- 5, respectively) were significantly lower than those in the hypoxic group (36 +/- 12 and 59 +/- 13, respectively, t = 4.89, 5.89, P < 0.05). The positive staining of ROCKI and ROCKII on pulmonary arterioles in the preventive group (1.18 +/- 0.10 and 1.30 +/- 0.12, respectively) were significantly lower than those in the hypoxic group (1.29 +/- 0.08 and 1.63 +/- 0.24, respectively, t = 3.90, 5.82, P < 0.05). The positive staining of ROCKI mRNA and ROCKII mRNA in the preventive group (1.23 +/- 0.13 and 1.22 +/- 0.06, respectively) were significantly lower than those in the hypoxic group (1.37 +/- 0.13 and 1.59 +/- 0.31, respectively, t = 3.94, 5.83, P < 0.05). CONCLUSION: Breviscapine was shown to prevent hypoxic pulmonary hypertension and decrease Rho-kinase and Rho-kinase mRNA.

[The change of fractalkine in lung tissue of rat with hypoxic pulmonary hypertension].

OBJECTIVE: To evaluate the role of fractalkine in the pathogenesis of hypoxic pulmonary hypertension. METHODS: Twenty male SD rats were randomly divided into control group and hypoxic group. Rats in hypoxic group were exposed to hypoxia for 3 weeks. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization. The thickness of pulmonary arterioles was measured with a computerized image analyzer. The rates of wall thickness/external diameter (WT%) and wall area/total vascular area (WA%) were calculated. The fractalkine level in lung tissue were measured by enzyme-linked immunosorbent assay. Fractalkine mRNA expression in lung were observed by reverse transcriptase-polymerase chain reaction. RESULTS: The rat mPAP of hypoxic group was higher than that of the control group [(28.7 +/- 3.8) mmHg vs (16.3 +/- 2.1) mmHg, P < 0.01]. The WT% and WA% were increased significantly in hypoxic group than in control group (WT%: (21.28 +/- 4.60)% vs (10.20 +/- 1.56)%, WA%: (67.08 +/- 9.44)% vs (38.11 +/- 42.30)%, P < 0.01, respectively]. In hypoxic group, the expression of fractalkine mRNA in the lung was significantly up-regulated [(0.49 +/- 0.05) vs (0.29 +/- 0.02), P < 0.01], the expression level of fractalkine in lung tissue was higher than that in control group [(7622.6 +/- 938.4) pg/mL vs (4168.5 +/- 403.5) pg/mL, P < 0.01. Linear correlation analyses showed that fractalkine mRNA and protein were positively associated with WA% and WT% (P < 0.05). CONCLUSION: The synthesis and release of fractalkine are increase in the lung tissue of chronic hypoxic rats, and fractalkine may play an important role in hypoxic pulmonary hypertension.

[The prophylactic effect of thymosin alpha 1 on the acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVES: To investigate the prophylactic effect of thymosin alpha 1 and its mechanism on patients with chronic obstructive pulmonary disease. METHODS: Eighty patients with chronic obstructive pulmonary disease were divided into two groups. In the treatment group, 42 patients received thymosin alpha 1 1.6 mg hypodermic injection, quague die alterna, for 10 times. All patients were followed for 6 months, and were assessed the number and days of patients with acute exacerbation at 3 and 6 months. In two groups, before treatment and 3 and 6 months after treatment, the pulmonary function tests were measured, and the blood samples were collected for the measurement of the blood IgA, IgG, IgM, CD3, CD4 and CD8 levels. RESULTS: In the treatment group, the number and days of patients with acute exacerbation were significantly lower in comparison with those of the control group. After treatment of thymosin alpha 1, blood CD4 and CD4/CD8 levels were significantly increased. CONCLUSION: Thymosin alpha 1 has a good protection for the acute exacerbation of chronic obstructive pulmonary disease, by incresing body cellular immune activity.

[Effect of dragon's blood on TGF-beta/smads signal transduction molecule mRNA expression in the lung tissue of rats with pulmonary fibrosis].

OBJECTIVE: To investigate the effect of Dragon's Blood on the expression of TGF-beta signal transduction molecule TGFbetaR II or Smad4 mRNA in the lung tissue of rats with pulmonary fibrosis, and to evaluate the effect and its mechanism of Dragon's Blood on pulmonary fibrosis. METHODS: 30 SD rats were randomly divided into three groups: fibrosis model, treatment and normal control groups. In model group and treatment group, the pulmonary fibrous tissues were induced to form with the intratracheal injection of bleomycin (5 mg/kg). In normal control group, saline was given intratracheally. Dragon's Blood was administered intragastricly in treatment group with a dose of 180 mg/kg diluted in 2 mL saline while saline was given intragastricly to other two groups with same volume from day 2 till day 28 after modeling. All rats were sacrificed on the 29th day. The rat lung histopathology was examined with HE staining. In situ hybridization was used to detect the expressions of TGFbetaR II and Smad4 mRNAs in lung tissue, and the expression of collagen fibril I was examined by an immunohistochemical staining. RESULTS: The inflammation cell counting in treatment group (12913.78 +/- 5640.12) was significant lower than that in model group (22243.60 +/- 5011.55, P < 0.01). The expression of pulmonary TGF/betaR II mRNA in treatment group was significant lower than that in model group (P < 0.01). In the Smad4 mRNA expression of lung tissue, there was no significant difference occurring between treatment group and model group (P > 0.05). The expression of collagen fibril I in the lung tissue of rats in treatment group was significant lower than that in model group (P < 0. 01). CONCLUSION: Dragon's Blood can effectively reduce rats' pulmonary fibrosis, of which the mechanisms may be to inhibit the expression of TGFbetaR II mRNA in the lung tissue and thus to have the preventive effect on the excessive deposit of collagen fibril I.

Association between serum interleukin-6 concentrations and chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Background. Interleukin-6 (IL-6) is an important pro-inflammatory cytokine and has been implicated to play a role in the systemic inflammation of patients with chronic obstructive pulmonary disease (COPD). We conducted this meta-analysis to assess the association between serum IL-6 concentrations and COPD. Methods. PubMed and Embase were searched for eligible studies. Data were extracted by two investigators (Wei J, Xiong XF) independently and analyzed using Review Manager 5.3 and STATA 12.0 software. Standard mean differences (SMDs) and 95% confidence intervals (CI) were calculated. Results. Thirty-three studies were included in this meta-analysis. The serum IL-6 concentrations were higher in patients with stable COPD than healthy controls (SMD = 0.65, 95% CI [0.51-0.79]). COPD patients without major comorbidities also showed higher IL-6 levels than healthy controls (SMD = 0.74, 95% CI [0.56-0.91]). COPD patients with an forced expiratory volume in one second (FEV1) of either <50% predicted or >50% predicted had increased IL-6 concentrations compared to healthy controls (SMD = 0.77, 95% CI [0.48-1.05], SMD = 1.01, 95% CI [0.43-1.59], respectively). The serum IL-6 concentrations between mild-moderate and severe-very severe COPD patient groups were not found to be significant (SMD = -0.1, 95% CI [-0.65-0.44]). Conclusions. This meta-analysis indicated that patients with stable COPD had higher serum IL-6 concentrations than healthy controls. No evidence showing positive or negative association between IL-6 concentrations and the severity of pulmonary function impairment was found. The correlation between IL-6 levels and pulmonary function was weak in different severities of stable COPD patients.

Association between TGFB1 915G/C polymorphism and susceptibility to chronic hepatitis C virus infection: A meta-analysis.

The human transforming growth factor-ß1 (TGF-ß1) gene, namely TGFB1, contains several single-nucleotide polymorphisms (SNPs) and some of the polymorphic variants were shown to affect the TGF-ß1 protein levels. A number of studies reported the association between 915G/C polymorphism and susceptibility to chronic hepatitis C virus (HCV) infection. However, the results were inconsistent. This meta-analysis was conducted to assess the association of TGFB1 915G/C polymorphism with susceptibility to chronic HCV infection. PubMed, ISI Web of Knowledge, ScienceDirect and Google Scholar databases were systematically searched up to August, 2013 to identify relevant studies. The pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were calculated in 5 genetic comparison models (C vs. G, CC vs. GG, GC vs. GG, CC vs. GG+GC and CC+GC vs. GG). The Galbraith plot and subgroup analyses based on ethnicity, genotyping methods, sample size and fibrosis were performed to investigate possible sources of heterogeneity. A sensitivity analysis and assessment of publication bias were also conducted. Finally, 8 eligible case-control studies on TGFB1 915G/C polymorphism, including a total of 910 cases and 632 controls, were included in this meta-analysis. Overall, there was no evidence of any gene-disease association obtained from the subgroup analyses. Therefore, this meta-analysis demonstrated that there is no association between TGFB1 915G/C polymorphisms and susceptibility to chronic HCV infection.