[Prevalence and intervention effect of arteriovenous graft stenosis].

Objective: To evaluate the prevalence, intervention methods and effect of arteriovenous graft (AVG) stenosis. Methods: The clinical data of patients who received AVG in the Blood Purification Center, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively analyzed. The patency rate, prevalence and intervention effect of AVG stenosis were analyzed. Results: A total of 475 patients aged (55.5±11.8) years were included, and there were 193 male cases (40.6%) and 282 female cases (59.4%). The patients were followed up for [M (Q1, Q3)] 19 (12, 30) months, and the primary, assisted primary and secondary patency were 14 (5, 27), 27 (13, 55), and 59 (33, 65) months, respectively. There were 799 access events which needed intervention, with a total standardized intervention rate of 0.90 per patient-year. Totally, 431(53.9%, 431/799) stenosis events occurred in 207 AVG. Among 422 AVG stenosis events with complete clinical data, 57.8% (244/422) were multi-site stenosis and 42.2% (178/422) were single-site stenosis. The most common sites of stenosis were graft-vein anastomosis (47.6%, 340/715), venous outflows (22.7%, 162/715), and puncture zone (20.0%, 143/715). In the 414 stenosis with intact follow-up data, 90.8% (376/414) were treated by balloon angioplasty, 8.5% (35/414) received covered stent insertion, and 0.7% (3/414) were intervened by open surgery. Clinical success rate was 98.1% (406/414). The primary patency time after endovascular treatment was 6 (4, 12) months. Covered stent significantly increased post-intervention primary patency time compared withballoon angioplasty [6 (3, 7) months vs 3 (1, 4) months, P=0.020]. Conclusions: Stenosis is the most common complication of AVG, and the most common sites are graft-vein anastomosis, venous outflows, and puncture zone. Intervention of AVG stenosis has a high clinical success rate, and a relatively low post-intervention patency. Covered stent insertion improves the post-intervention patency of AVG, which has a poor effect using balloon expansion.

[The reconstruction techniques and mid-term clinical outcomes of hip revision for acetabular bone defect after total hip arthroplasty].

Objective: To analyze three reconstruction techniques and mid-term clinical outcomes of hip revision for acetabular bone defect after total hip arthroplasty (THA). Methods: This is a retrospective case series study. Included in the study were 109 patients (109 hips) with acetabular bone defect after THA reconstructions in hip revisions from January 2015 to December 2021 in the Senior Department of Orthopaedics, the Forth Medical Center of Chinese People's Liberation Army General Hospital and the Department of Orthopaedics, the First Medical Center of Chinese People's Liberation Army General Hospital. According to the preoperative simulated surgeries and different bone defect reconstruction techniques, patients were divided into a normal cup group, an augment group or a triflange group,respectively. There were 54 patients (54 hips) in the normal cup group, reconstructed with the uncemented porous metal cup (including Jumbo cup), with 23 males and 31 females, aged (59.6±9.9) years (range:32 to 76 years); 44 patients (44 hips) in the augment group, reconstructed with the individualized three-dimensional (3D) printed porous metal augment and uncemented porous metal cup, with 18 males and 26 females, aged (52.8±13.6) years(range:17 to 76 years); 11 patients (11 hips) in the triflange group, reconstructed by the individualized 3D printed porous metal triflange cup, with 5 males and 6 females, aged (59.4±11.2) years (range: 43 to 78 years). Radiographic results, including rotation center height, rotation center offset, and leg length discrepancy (LLD) and clinical results, including Harris hip score (HHS) and visual analogue scale(VAS) were evaluated outpatient at 3, 6, 12 months after the operation and annually thereafter. The last follow-up was completed in March 2024, and all parameters at the last follow-up and before the operation were compared. Paired sample t test and repeated measurement ANOVA were used for the radiographic and clinical parameters before and after the operation. Results: All hip revisions for patients with acetabular bone defect after THA were completed and followed for more than two years. The follow-up time of the normal cup group was (6.5±1.7) years (range: 2.8 to 9.3 years), and that of the augment group was (6.0±1.3) years (range: 3.5 to 9.0 years). The follow-up time of the triflange group was (2.8±0.6) years (range: 2.0 to 3.8 years). At the last follow-up, the rotation center height, rotation center offset and LLD of 54 hips in the normal cup group were (24.2±5.6) mm, (29.1±5.5) mm and (4.6±3.3) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips (t=9.671, P<0.01; t=6.073, P<0.01). In the augment group, the rotational center height, the rotation center offset and the LLD of 44 hips were (22.4±9.0) mm, (25.4±5.5) mm and (6.0±4.0) mm, respectively, which were significantly lower than those of the preoperative hips (t=9.071, P<0.01; t=11.345, P<0.01; t=4.927, P<0.01). In the triflange group, the rotational center height, the rotation center offset and LLD of 11 hips were (22.7±6.0) mm,(30.9±8.0) mm and (5.3±2.2) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips (t=2.716, P=0.022; t=6.226, P<0.01). At the last follow-up, fractures occurred in 3 patients and dislocation occurred in 1 patient in the normal cup group, and fracture reduction and closed reduction were administered under anesthesia, respectively. In the augment group, dislocation occurred in 1 patient and open reduction under anesthesia was performed. The HHS and VAS of the three groups improved significantly after surgery and the differences were statistically significant (all P<0.01). There was no complication in the triflange group. The X-ray at the last follow-up showed that all prostheses and augments were in stable positions and no loosening or migration was observed. Conclusions: For patients with acetabular bone defect after THA undergoing hip revisions, preoperative surgical simulation and rehearsal could help surgeons choose convenient and efficient reconstruction techniques. The targeted selection of Jumbo cup, individualized 3D printed metal augment, and customized triflange cup could achieve satisfactory clinical outcomes.

MicroRNA-206 inhibits tumor metastasis of nasopharyngeal carcinoma through targeting G6PD.

Nasopharyngeal carcinoma (NPC) is a main type of otolaryngological malignancy. In many cancers, miR-206 functions as a tumor suppressor, suppressing cell proliferation, migration and invasion. The purpose of this study was to explore how miR-206 worked on cell metastasis in NPC. The mRNA levels of miR-206 and G6PD were determined in NPC tissues and cell lines by RT-qPCR and Western blot. Transwell assay was applied to evaluate the migratory and invasive capacities. Dual luciferase reporter assay was employed to confirm that miR-206 mediated the expression of G6PD in C666-1 cells. In this study, miR- 206 was downregulated, whereas G6PD was upregulated in NPC tissues and cell lines. In addition, G6PD was identified as a direct target gene of miR-206 in C666-1 cells. The expression of G6PD was mediated by miR-206, which could partially reverse the inhibitory effects of miR-206 on the migration, invasion and EMT in C666-1 cells. In conclusion, miR-206 regulated the migratory, invasive and EMT abilities through directly targeting the 3'-UTR of G6PD mRNA in C666-1 cells. The newly identified miR-206/G6PD axis provides novel insight into the pathogenesis of nasopharyngeal carcinoma.

Experimental Evidence of Kinetic Effects in Indirect-Drive Inertial Confinement Fusion Hohlraums.

We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (∼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (∼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.

[Genes and molecular mechanisms affecting the correlation between liver cancer and diabetes mellitus].

Hepatocellular carcinoma (HCC) is a common and high incidence disease in China. It is presently thought that diabetes is one of the independent risk factor for HCC. Diabetes and liver cancer are closely related, but the relationship and mechanism of diabetes and liver cancer are quite complex and controversial. Insulin resistance, glucose metabolism and lipid metabolism disorders, and abnormal release of inflammatory mediators are the common bases of these two diseases. The molecular mechanisms of glycogen synthase kinase-3, toll like receptor 4, CCL5, CXCL14 and NCOA5, TCF7L2 genes affecting the correlation between liver cancer and diabetes mellitus are discussed and explained to provide the basis for the study and treatment of disease.

New insights from GWAS for the cleft palate among han Chinese population.

BACKGROUND: Genome wide association studies (GWAS) already have identified tens of susceptible loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, whether these loci associated with nonsyndromic cleft palate only (NSCPO) remains unknown. MATERIAL AND METHODS: In this study, we replicated 38 SNPs (Single nucleotide polymorphisms) which has the most significant p values in published GWASs, genotyping by using SNPscan among 144 NSCPO trios from Western Han Chinese. We performed the transmission disequilibrium test (TDT) on individual SNPs and gene-gene (GxG) interaction analyses on the family data; Parent-of-Origin effects were assessed by separately considering transmissions from heterozygous fathers versus heterozygous mothers to affected offspring. RESULTS: Allelic TDT results showed that T allele at rs742071 (PAX7) (p=0.025, ORtransmission=3.00, 95%CI: 1.09-8.25) and G allele at rs2485893 (10kb 3' of SYT14) were associated with NSCPO (p=0.0036, ORtransmission= 0.60, 95%CI: 0.42-0.85). Genotypic TDT based on 3 pseudo controls further confirmed that rs742071 (p-value=0.03, ORtransmission=3.00, 95%CI: 1.09-8.25) and rs2485893 were associated with NSCPO under additive model (p-value= 0.02, ORtransmission= 0.66, 95%CI: 0.47-0.92). Genotypic TDT for epistatic interactions showed that rs4844913 (37kb 3' of DIEXF) interacted with rs11119388 (SYT14) (p-value=1.80E-08) and rs6072081 (53kb 3' of MAFB) interacted with rs6102085 (33kb 3' of MAFB) (p-value=3.60E-04) for NSCPO, suggesting they may act in the same pathway in the etiology of NSCPO. CONCLUSIONS: In this study, we found that rs742071 and rs2485893 were associated NSCPO from Han Chinese population; also, interactions of rs4844913:rs11119388 and rs6072081:rs6102085 for NSCPO were identified, gene-gene interactions have been proposed as a potential source of the remaining heritability, these findings provided new insights of the previous GWAS.

Association between miR-137 polymorphism and risk of schizophrenia: a meta-analysis.

miR-137, a brain-enriched microRNA, is involved in the control of neuronal proliferation, differentiation, and dendritic arborization, all of which are important for proper neurogenesis and relevant to schizophrenia. miR-137 is also known to regulate many genes implicated in schizophrenia risk. Although reports have associated the miR-137 polymorphism rs1625579 with this disease, their results have been inconsistent. The aim of this meta-analysis was to evaluate the relationship between rs1625579 and schizophrenia. Data were obtained from an electronic database, and pooled odds ratios (ORs) with 95% confidence intervals (95%CI) were used to test the association using the RevMan 5.3 software. Twelve case-control studies comprising 11,583 cases and 14,315 controls were included. An estimated lambda value of 0.46 was recorded, suggesting that a codominant model of inheritance was most likely. A statistically significant association was established under allelic (T vs G: OR = 1.15, 95%CI = 1.10-1.21, P < 0.001) and homogeneous codominant models (TT vs GG: OR = 1.32, 95%CI = 1.13-1.54, P < 0.001), but no such relationship was detected using the heterogeneous codominant model (GT vs GG: OR = 1.14, 95%CI = 0.97-1.34, P = 0.11). This meta-analysis demonstrates that the rs1625579 miR-137 genetic variant significantly increases schizophrenia risk.

Association between IL2/IL21 and SH2B3 polymorphisms and risk of celiac disease: a meta-analysis.

Celiac disease (CD) is a common autoimmune disorder characterized by heightened immunological response to ingested gluten. Certain gene polymorphisms of IL2/IL21 (rs6822844 and rs6840978) and SH2B3 (rs3184504) may influence susceptibility to CD, although the effects remain unclear. We performed a meta-analysis of the associations between rs6822844, rs6840978, and rs3184504 polymorphisms and CD risk. PubMed, EMBASE, and the China National Knowledge Infrastructure were searched. ORs and 95%CIs of each single nucleotide polymorphism (SNP) were estimated using the fixed-effect model if I(2) < 50% in the test of heterogeneity; otherwise, the random-effect model was used. Our meta-analysis included 12,986 CD cases and 28,733 controls from 16 independent samples, and the analysis of each SNP contained a subset of the total. We found that the minor allele T of both rs6822844 (T vs G, OR = 0.72, 95%CI = 0.67-0.78, P < 0.001) and rs6840978 (T vs C, OR = 0.76, 95%CI = 0.71-0.83, P < 0.001) in IL2/IL21 significantly decreased the risk of CD. However, the minor allele A of rs3184504 (A vs G, OR = 1.18, 95%CI = 1.12-1.24, P < 0.001) in SH2B3 significantly increased CD susceptibility. The estimated lambda values were 0.49, 0.50, and 0.53 for rs6822844, rs6840978, and rs3184504, respectively, suggesting that a co-dominant model of genotype effect was most appropriate for the three SNPs. Our results support associations between the three SNPs and CD and provide a strong argument for further research.

Association of TLR2 and TLR4 non-missense single nucleotide polymorphisms with type 2 diabetes risk in a southern Chinese population: a case-control study.

Toll-like receptors (TLRs), the triggers of the innate and adaptive immune responses, are involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Several studies have investigated the effects of genetic polymorphisms in TLR4 and TLR2, but they have yielded limited results. We investigated whether non-missense genetic polymorphisms in the regulatory regions of TLR4 and TLR2 were related to T2DM in a southern Chinese population. Single nucleotide polymorphisms (SNPs) in TLR4 (rs1927911, rs11536889, rs1927907, rs1927906, rs1927914, rs7873784, and rs2149356) and TLR2 (rs1898830, rs3804099, rs4696480, and rs3804100) were genotyped in 552 T2DM and 552 unrelated age- and gender-matched controls by SNaPShot Multiplex assay. Genotypes GG (OR = 0.09, 95%CI = 0.01- 0.83, P = 0.03) and CG (OR = 0.08, 95%CI = 0.01-0.74, P = 0.03) of the 3'-untranslated region (UTR) SNP rs7873784 in TLR4, and genotype AG (OR = 0.67, 95%CI = 0.46-0.97, P = 0.04) and allele G (OR = 0.88, 95%CI = 0.79-0.97, P = 0.01) of the intron SNP rs1898830 in TLR2 were identified as protective against the development of T2DM in southern Chinese people. In contrast, a meta-analysis of rs1927911 and rs1927914 showed no association. Haplotypes AGTT (OR = 0.34, 95%CI = 0.15-0.77, P = 0.01) and AATT (OR = 1.20, 95%CI = 1.01- 1.44, P = 0.05) in TLR2 were significantly associated with susceptibility to T2DM. Our results suggest that the effects of non-missense polymorphisms located in the regulatory regions of TLR4 and TLR2 should not be neglected in T2DM association analysis.

Fragmentation mechanisms for methane induced by 55 eV, 75 eV, and 100 eV electron impact.

The fragmentation of CH4 (2+) dications following 55 eV, 75 eV, and 100 eV electron impact double ionization of methane was studied using a cold target recoil-ion momentum spectroscopy. From the measured momentum of each recoil ion, the momentum of the neutral particles has been deduced and the kinetic energy release distribution for the different fragmentation channels has been obtained. The doubly charged molecular ions break up into three or more fragments in one or two-step processes, resulting in different signatures in the data. We observed the fragmentation of CH4 (2+) dications through different mechanisms according to the momentum of the neutral particles. For example, our result shows that there are three reaction channels to form CH2 (+), H(+), and H, one synchronous concerted reaction channel and two two-step reaction channels. For even more complicated fragmentation processes of CH4 (2+) dications, the fragmentation mechanism can still be identified in the present measurements. The slopes of the peak in the ion-ion coincidence spectra were also estimated here, as they are also related to the fragmentation mechanism.

Esophageal leiomyosarcoma: clinical analysis and surgical treatment of 12 cases.

Leiomyosarcoma of the esophagus is a rare malignant tumor with slow growth and late metastasis. The aim of this study was to reassess the clinical characteristics and treatment modality in one of the largest series of esophageal leiomyosarcomas from a single institution. From February 1973 to December 2011, 12 cases of esophageal leiomyosarcoma were identified. The principal symptoms included progressive dysphagia in 11 cases (91.7%), retrosternal/back pain in four (33.3%), weight loss in four (33.3%), upper gastrointestinal hemorrhage in two (16.7%), and emesis in two (16.7%). The average duration of symptoms was 10.6 months. The location of the primary tumor was in the middle thoracic esophagus in five cases, and lower thoracic esophagus in seven cases. Six cases were classified as the polypoid type, five cases as the infiltrative type, and only one case as the intramural type. All 12 of the patients underwent esophagectomies, and radical resections were achieved in these patients. Based on the Kaplan-Meier Method, the 3-, 5-, and 10-year survival rates were 80.0%, 58.3%, and 31.1%, respectively, with a median survival of 63 months. Five-year survival rates for patients with polypoid or intramural tumors (n = 7) was 83.3%, and for patients with infiltrative tumor (n = 5) it was 25.0%. One of the patients had tumor resected four times and survived for 161 months. In conclusion, patients presenting with esophageal leiomyosarcomas have an excellent prognosis, and radical resection may achieve acceptable results.

QL1701 (a proposed trastuzumab biosimilar) versus reference trastuzumab plus docetaxel as first-line therapy for HER2-positive metastatic breast cancer: a multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial.

BACKGROUND: QL1701 is a proposed biosimilar to the reference trastuzumab (Herceptin®). This trial compared the efficacy and safety of QL1701 with the reference trastuzumab in first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. MATERIALS AND METHODS: This randomized, double-blinded, parallel-controlled, phase III equivalence trial was conducted in 73 centers in China. Eligible patients with histologically or cytologically diagnosed HER2-positive metastatic breast cancer were randomly assigned (1 : 1) to receive either QL1701 or reference trastuzumab in combination with docetaxel (every 3 weeks) for eight cycles as the first-line treatment. Then, in patients with objective responses or stable disease, the QL1701 or reference trastuzumab with or without docetaxel was maintained for totally up to 12 months if tolerated. The primary endpoint was 24-week objective response rate (ORR) assessed by an independent review committee (IRC). The equivalence margin was 0.80-1.25 with a 90% confidence interval (CI) for the ORR ratio (QL1701 to reference trastuzumab). RESULTS: Between 29 April 2020 and 15 March 2022, 474 patients were randomized, and 473 received either QL1701 (n = 236) or reference trastuzumab (n = 237). The risk ratio for 24-week ORR was 1.07 (90% CI 0.94-1.21). The 90% CI fell within the pre-specified equivalence margin of 0.80-1.25. The 24-week ORR assessed by IRC was 59.7% (95% CI 53.2% to 66.1%) versus 56.1% (95% CI 49.5% to 62.5%) in QL1701 and the reference trastuzumab, respectively. As of 12 April 2023, there were no notable differences in progression-free survival (median: 8.3 versus 8.4 months) and overall survival (1-year rate: 95.1% versus 93.3%) between the two groups. Safety, pharmacokinetic (PK), and immunogenicity profiles were similar between the two groups. CONCLUSION: QL1701 demonstrated equivalent efficacy and similar safety to the reference trastuzumab when combined with docetaxel in the first-line treatment of patients with HER2-positive metastatic breast cancer, with similar PK and immunogenicity profiles.

Prognostic value of peritumoral heat-shock factor-1 in patients receiving resection of hepatocellular carcinoma.

BACKGROUND: The cross-talk of hepatocellular carcinoma (HCC) cells and abnormal metabolic signals in peritumoral microenvironment modifies our knowledge of hepatocarcinogenesis. As an indispensable modulator of various stresses, the clinical significance of heat-shock transcription factor-1 (HSF1) in HCC microenvironment has never been defined. METHODS: Hepatocellular carcinoma and matched peritumoral liver tissues (n=332) were semiquantitatively analysed for HSF1 expression, followed by correlation with clinicopathological parameters (patient outcomes). Moreover, the effects of HSF1 deficiency in L02 on monocarboxylate transporter-4 (MCT4) and HCC cells' colonisation and proliferation were investigated. RESULTS: High expression of HSF1 in peritumoral tissue but not in HCC tissue was associated with poorer overall survival (OS) and time to recurrence (TTR), especially early recurrence (ER), which was further reconfirmed in validation cohort. Multivariate analysis showed that prognostic performance of peritumoral HSF1 was independent of other clinicopathological factors (hazard ratio for OS=2.60, P=0.002, for TTR=2.52, P<0.001). Notably, downregulation of HSF1 in L02 decreased MCT4 expression significantly. The supernatant from L02-shRNA-HSF1 in hypoxia, NOT normoxia condition, inhibited HCC cell colonisation and proliferation. Moreover, the combination of peritumoral HSF1 and MCT4 was the best predictor for ER and OS. CONCLUSION: High peritumoral HSF1 expression can serve as a sensitive 'readout' for high-risk HCC ER, and could be a potential metabolic intervention target following curative resection.

Living status in patients over 85 years of age after TUVRP.

INTRODUCTION: To evaluate surgical risk and post-operative quality of living status in patients over 85 years of age after transurethral vaporization resection of the prostate (TUVRP). METHODS: Sixty patients over 85 years of age underwent TUVRP were compared with 228 patients less than the age of 80 years. Group A was 60 patients greater than 85 years of age, Group B was 137 patients from 71 to 79 years of age, and Group C was 91 patients from 60 to 70 years of age. RESULTS: In Group A, pre-operative ASA grade was higher than the other two groups, compared with Group C, p < 0.01. Operating time was 40.03 ± 18.90 min, compared in the three groups, p > 0.05. Follow-up was obtained in 49 (81.67%) patients; of them 10 patients were deaths with a survival time of 22.90 ± 11.14 months. In the 39 survivors, post-operative IPSS score was 11.17 ± 6.9, compared with Group B, p > 0.05 and Group C, p < 0.01. Quality of Life (QOL) index was 1.11 ± 0.80, compared with Group B, p < 0.001 and Group C, p < 0.01. Barthel Index score in 16 patients was >60 and the score was 82.81 ± 8.56 pre-operatively. The patients with >60 were increased to 19 cases and the score was improved to 90.93 ± 7.58 (p < 0.001) in follow-up. CONCLUSION: Surgical risk in patients over 85 years of age was higher than patients less than the age of 80 years. A safety TUVRP could improve their voiding function and activities of daily living.

Analysis of differentially expressed genes in ductal carcinoma with DNA microarray.

AIM: The aim of this study is to investigate the dysregulated biological functions that play important role in the occurrence and development of breast invasive ductal carcinoma (IDC). MATERIALS AND METHODS: We downloaded the gene expression profile data from gene expression omnibus (GEO) database, including 42 disease samples and 143 adjacent histological normal samples. Significance analysis of microarrays (SAM) was employed to identify differentially expressed genes (DEGs) between the normal and disease samples. Gene ontology (GO) function enrichment analysis was based on Software DAVID, followed by KEGG pathway enrichment analysis. TRANSFAC database and HPRD database were employed to construct the transcriptional regulatory network (Tnet) and protein-protein interaction (PPI) network, respectively. RESULTS: We got a total of 1769 genes significantly differentially expressed, including 907 up-regulated genes and 862 down-regulated genes. Functional analysis revealed that hormone-responsive genes are related with the occurrence of cancer. Then, we successfully constructed IDC-specific Tnet and PPI network with DEGs response to hormone and obtained some hub genes, such as FOS and PIK3R1, in these networks. Besides, ten modules were found in these networks. CONCLUSIONS: Hormone-responsive genes and modules may play an important role in the occurrence and development of IDC. Based on the findings above, we got a preliminary understand of the occurrence, development and metastasis of the IDC and possibly provided effective information on the biogenesis of IDC.

[Study on the mechanism of early pancreatic exocrine function changes in severely scalded rats].

Objective: To explore the mechanism of early pancreatic exocrine function changes in severely scalded rats. Methods: The experimental research methods was used. Eighty male Sprague-Dawley rats aged 7-8 weeks were divided into simple sham injury group (n=8), sham injury+cholecystokinin octapeptide (CCK8) group (n=8), severe scald+CCK8 group (n=32), and extremely severe scald+CCK8 group (n=32) by the random number table, which were treated accordingly. Immediately after injury of rats in the 2 sham injury groups and 1, 2, 3, and 7 days after injury of rats in the 2 scald groups, the improved methods including pancreatic duct puncture and catheterization were used to dynamically collect the pancreatic-bile juice (PBJ) of rats. The PBJ secretory volume within 1 h was recorded, and the content of pancreatic lipase, α-amylase, and trypsin in PBJ was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 8. The femoral venous blood was collected, and the concentrations of pancreatic lipase and α-amylase in serum were detected by standard colorimetry to reflect their activity (n=8). The pancreatic tissue was extracted, and the levels of interleukin-1ß (IL-1ß) and IL-6 in pancreatic tissue were detected by ELISA (n=8), the expression of hypoxia-inducible factor 1α (HIF-1α) in pancreatic tissue was detected by immunofluorescence method, and the histopathological changes in pancreatic tissue were observed by hematoxylin-eosin staining, the severity of pancreatic tissue injury in the 2 scald groups was evaluated by modified Schmidt method (n=6), and the ultrastructure of acinar cells in pancreatic tissue was observed by transmission electron microscopy. Data were statistically analyzed with analysis of variance for factorial design, Tukey test, independent sample t test, and least significant difference test. Results: Compared with the PBJ secretory volume (0.740±0.030) mL in the pancreatic tissue of rats in simple sham injury group within 1 h immediately after injury, the (0.823±0.033) mL in sham injury+CCK8 group was significantly increased (t=4.92, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the PBJ secretory volume of rats within 1 h in severe scald+CCK8 group ((0.681±0.024), (0.608±0.056), (0.525±0.025), and (0.720±0.044) mL) and extremely severe scald+CCK8 group ((0.540±0.025), (0.406±0.021), (0.475±0.036), and (0.690±0.018) mL) was significantly decreased on 1, 2, 3, and 7 days after injury (P<0.05). Compared with that in severe scald+CCK8 group, the PBJ secretory volume of rats within 1 h in extremely severe scald+CCK8 group was significantly decreased on 1 and 2 days after injury (P<0.05). Compared with that of rats in simple sham injury group immediately after injury, the content of pancreatic lipase, α-amylase, and trypsin in PBJ of rats in sham injury+CCK8 group immediately after injury was significantly increased (with t values of 4.56, 3.30, and 4.99, respectively, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the content of pancreatic lipase and α-amylase in PBJ of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group was significantly decreased on 1, 2, 3, and 7 days after injury (P<0.05), the trypsin content in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 2 days after injury (P<0.05). Compared with that in severe scald+CCK8 group, the content of pancreatic lipase in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 1, 2, and 3 days after injury (P<0.05), and the content of α-amylase and trypsin in PBJ was significantly decreased on 1 and 2 days after injury (P<0.05). There were no statistically significant differences in the activities of pancreatic lipase and α-amylase in serum of rats among the 4 groups at various time points after injury (P>0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the levels of IL-1ß in pancreatic tissue of rats in severe scald+CCK8 group on 1, 2, and 3 days after injury and in extremely severe scald+CCK8 group on 1, 2, 3, and 7 days after injury were significantly increased (P<0.05), and the levels of IL-6 in pancreatic tissue of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group were significantly increased on 1, 2, 3, and 7 days after injury (P<0.05). Compared with that in severe scald+CCK8 group, the IL-1ß level in pancreatic tissue of rats in extremely severe scald+CCK8 group was significantly increased on 2 and 3 days after injury (P<0.05), and IL-6 level in pancreatic tissue was significantly increased on 2 days after injury (P<0.05). The expression levels of HIF-1α in pancreatic tissue of rats in simple sham injury group and sham injury+CCK8 group immediately after injury were lower; and compared with that in sham injury+CCK8 group immediately after injury, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups increased to a certain extent at different time points after injury, and the expression position was transited from the edge of the pancreatic tissue to the whole pancreas, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups tended to be normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the proportion of acinar cell cytoplasm in pancreatic tissue of rats in sham injury+CCK8 group was increased; and with the increase of time after injury, edema, hemorrhage, necrosis, and inflammatory infiltration appeared in pancreatic tissue of rats in the 2 scald groups. Compared with that in severe scald+CCK8 group, the scores of edema, inflammatory cell infiltration, bleeding, and necrosis in pancreatic tissue of rats in extremely severe scald+CCK8 group were increased to varying degrees at various time points after injury, and the scores of pancreatic tissue of rats in the 2 scald groups basically recovered to normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the number of enzyme granules in acinar cells of pancreatic tissue of rats in sham injury+CCK8 group was increased, and with the increase of time after injury, the enzyme granules in acinar cells of rats in the 2 scald groups were gradually reduced basically. Conclusions: The exocrine functions of pancreas, such as synthesis and secretion of pancreatic enzymes, are decreased in the early stage in severely scalded rats. And the greater the scalded area, the more significant the decline of pancreatic exocrine function. This change may be related to hypoxic injury and inflammation in pancreatic tissue after severe scald.

[Establishment and application of the ten-fold rehydration formula for emergency resuscitation of pediatric patients after extensive burns].

Objective: To investigate the scientificity and feasibility of the ten-fold rehydration formula for emergency resuscitation of pediatric patients after extensive burns. Methods: A retrospective observational study was conducted. The total burn area of 30%-100% total body surface area (TBSA) and body weight of 6-50 kg in 433 pediatric patients (250 males and 183 females, aged 3 months to 14 years) with extensive burns who met the inclusion criteria and admitted to the burn departments of 72 Class A tertiary hospitals were collected. The 6 319 pairs of simulated data were constructed after pairing each body weight of 6-50 kg (programmed in steps of 0.5 kg) and each total burn area of 30%-100% TBSA (programmed in steps of 1%TBSA). They were put into three accepted pediatric rehydration formulae, namely the commonly used domestic pediatric rehydration formula for burn patients (hereinafter referred to as the domestic rehydration formula), the Galveston formula, and the Cincinnati formula, and the two rehydration formulae for pediatric emergency, namely the simplified resuscitation formula for emergency care of patients with extensive burns proposed by the World Health Organization's Technical Working Group on Burns (TWGB, hereinafter referred to as the TWGB formula) and the pediatric ten-fold rehydration formula proposed by the author of this article--rehydration rate (mL/h)=body weight (kg) × 10 (mL·kg-1·h-1) to calculate the rehydration rate within 8 h post injury (hereinafter referred to as the rehydration rate). The range of the results of the 3 accepted pediatric rehydration formulae ±20% were regarded as the reasonable rehydration rate, and the accuracy rates of rehydration rate calculated using the two pediatric emergency rehydration formulae were compared. Using the maximum burn areas (55% and 85% TBSA) corresponding to the reasonable rehydration rate calculated by the pediatric ten-fold rehydration formula at the body weight of 6 and 50 kg respectively, the total burn area of 30% to 100% TBSA was divided into 3 segments and the accuracy rates of the rehydration rate calculated using the 2 pediatric emergency rehydration formulae in each segment were compared. When neither of the rehydration rates calculated by the 2 pediatric emergency rehydration formulae was reasonable, the differences between the two rehydration rates were compared. The distribution of 433 pediatric patients in the 3 previous total burn area segments was counted and the accuracy rates of the rehydration rate calculated using the 2 pediatric emergency rehydration formulae were calculated and compared. Data were statistically analyzed with McNemar test. Results: Substitution of 6 319 pairs of simulated data showed that the accuracy rates of the rehydration rates calculated by the pediatric ten-fold rehydration formula was 73.92% (4 671/6 319), which was significantly higher than 4.02% (254/6 319) of the TWGB formula (χ2=6 490.88,P<0.05). When the total burn area was 30%-55% and 56%-85% TBSA, the accuracy rates of the rehydration rates calculated by the pediatric ten-fold rehydration formula were 100% (2 314/2 314) and 88.28% (2 357/2 670), respectively, which were significantly higher than 10.98% (254/2 314) and 0 (0/2 670) of the TWGB formula (with χ2 values of 3 712.49 and 4 227.97, respectively, P<0.05); when the total burn area was 86%-100% TBSA, the accuracy rates of the rehydration rates calculated by the pediatric ten-fold rehydration formula and the TWGB formula were 0 (0/1 335). When the rehydration rates calculated by the 2 pediatric emergency rehydration formulae were unreasonable, the rehydration rates calculated by the pediatric ten-fold rehydration formula were all higher than those of the TWGB formula. There were 93.07% (403/433), 5.77% (25/433), and 1.15% (5/433) patients in the 433 pediatric patients had total burn area of 30%-55%, 56%-85%, and 86%-100% TBSA, respectively, and the accuracy rate of the rehydration rate calculated using the pediatric ten-fold rehydration formula was 97.69% (423/433), which was significantly higher than 0 (0/433) of the TWGB formula (χ2=826.90, P<0.05). Conclusions: The application of the pediatric ten-fold rehydration formula to estimate the rehydration rate of pediatric patients after extensive burns is more accurate and convenient, superior to the TWGB formula, suitable for application by front-line healthcare workers that are not specialized in burns in pre-admission rescue of pediatric patients with extensive burns, and is worthy of promotion.

[The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia].

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) µg/L, and 54% (14/26) of these patients had SF levels of ≥100 µg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) µg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 µg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

A Variant in the IRF6 Promoter Associated with the Risk for Orofacial Clefting.

The single-nucleotide polymorphism (SNP) rs2235371 (IRF6 V274I) is associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Han Chinese and other populations but appears to be without a functional effect. To find the common etiologic variant or variants within the haplotype tagged by rs2235371, we carried out targeted sequencing of an interval containing IRF6 in 159 Han Chinese with NSCL/P. This study revealed that the SNP rs12403599, within the IRF6 promoter, is associated with all phenotypes of NSCL/P, especially nonsyndromic cleft lip (NSCLO) and a subphenotype of it, microform cleft lip (MCL). This association was replicated in 2 additional much larger cohorts of cases and controls from the Han Chinese. Conditional logistic analysis indicated that association of rs2235371 with NSCL/P was lost if rs12403599 was excluded. rs12403599 contributes the most risk to MCL: its G allele is responsible for 38.47% of the genetic contribution to MCL, and the odds ratios of G/C and G/G genotypes were 2.91 and 6.58, respectively, for MCL. To test if rs12403599 is functional, we carried out reporter assays in a fetal oral epithelium cells (GMSM-K). Unexpectedly, the risk allele G yielded higher promoter activity in GMSM-K. Consistent with the reporter studies, expression of IRF6 in lip tissues from NSCLO and MCL patients with the G/G phenotype was higher than in those from patients with the C/C phenotype. These results indicate that rs12403599 is tagging the risk haplotype for NSCL/P better than rs2235371 in Han Chinese and supports investigation of the mechanisms by which the allele of rs12403599 affects IRF6 expression and tests of this association in different populations.