Evaluation of complications associated with bifocal bone transport as treatment for either proximal, intermediate or distal femoral defects caused by infection: outcome analysis of 76 patients.

BACKGROUND: The purpose of this study was to evaluate the outcomes of bifocal bone transport in the treatment of femoral bone defects caused by infections. METHODS: Clinical and radiographic data of patients with infected femoral nonunion treated by the bifocal bone transport at our hospital were analyzed retrospectively, from January 2008 to December 2019. Depending on the location of bone defects, the patients were divided into three groups (proximal, intermediate, and distal). The Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria was applied to assess the bone and functional outcomes. Postoperative complications of three groups were documented and compared. RESULTS: Seventy-six cases of infected femoral bone defects (31 cases of proximal, 19 cases of intermediate, and 26 cases of distal) were managed by bifocal bone transport successfully with a mean follow-up time of 30.8 months (range, 23 to 41 months). There were 58 men (76.3%) and 18 women (23.6%), with a mean age of 38.8 years (range, 23 to 60 years). The bone union was received in 76 cases with a mean of 6.9 months (range, 5 to 8 months). Pin tract infection was observed in twenty-nine cases (38.1%), 7 cases (9.2%) of muscle contractures, 3 cases (7.9%) of joint stiffness, 13 cases (17.1%) of axial deviation, 2 cases (2.6%) of delayed union, one case (1.3%) of nonunion, and none (0%) of transport gap re-fracture. One patient (1.3%) was scheduled for knee arthroplasty when bone transport treatment ended. CONCLUSIONS: Bone transport using an external rail fixator was a practical method to treat the femoral bone defects, since the satisfactory rate of bone union and limb function recovery. Complications of distal femoral bone transport were more severe than the proximal and intermedia, but the rate of complication was the least of the three groups. Soft-tissue-related complications were more likely to occur in the intermediate bone transport.

Evaluation of sparing the pronator quadratus for volar plating of distal radius fractures: a retrospective clinical study.

BACKGROUND: The most commonly used approach for distal radius fractures is the traditional Henry approach. However, it requires an intraoperative incision of the pronator quadratus (PQ) muscle, which results in a series of complications if the repair of the PQ fails. AIM: The objective of this study was to investigate the efficacy of sparing the pronator quadratus for volar plating of the distal radius fractures. METHODS: Seventy-six patients who suffered from distal radius fractures of types 23-B, 23-C1, and 23-C2 as per the AO Foundation and Orthopaedic Trauma Association (AO/OTA) classification were treated with volar locking plate fixation using either the PQ muscle incision and repair (group A, n = 39) or the PQ muscle preservation approach (group B, n = 37). Intraoperative index, postoperative efficacy and complications of patients were recorded and evaluated. RESULTS: All patients were followed up for more than one year after surgery. All fractures achieved union. There were significant differences in mean operative time, mean intraoperative blood loss, and mean fracture healing time between the two groups. Still, there were no significant differences in limb function scores between the two groups at the 12-month postoperative follow-up. Outcomes assessed at 1 week, 1 month, and 3 months after surgery demonstrated significant differences in the mean range of motion and pain-related visual analog scale (VAS) between the two groups. As the range of motion and grip strength increased, the VAS scores decreased, and there was no significant difference between the two groups at 12 months postoperatively. Although tendon irritation and delayed carpal tunnel syndrome were more common in group A than in group B (7.6% vs. 0% and 5.1% vs. 0%, respectively), the differences were not statistically significant. CONCLUSION: The modified Henry approach with sparing pronator quadratus muscle has no significant advantage in the range of wrist motion and upper limb function in the late stage. Nevertheless, the intraoperative placement of the plate under the pronator quadratus muscle can shorten the operation time, reduce intraoperative bleeding, reduce early postoperative pain, promote early activity, and improve the patient's quality of life. It is recommended that the pronator be preserved at the time of surgery.

Flexible calibration method for telecentric fringe projection profilometry systems.

A newly developed flexible calibration algorithm for telecentric 3D measurement systems is presented in this paper. We theoretically analyzed the similarities and differences between the telecentric and entocentric system. The telecentric system can be calibrated with the aid of the traditional 2D planar calibration method. An additional two-step refining process is proposed to improve the calibration accuracy effectively. With the calibration and refining algorithm, an affine camera can be calibrated with a reprojection error of 0.07 pixel. A projector with small field of view (FOV) is applied to achieve a full 3D reconstruction in our profilometry system. Experiments with a prototype demonstrate the validation and accuracy of the proposed calibration algorithm and system configuration. The reconstruction accuracy can achieve 5 µm with a measurement FOV of 28.43 mm×21.33 mm and a working distance of 110 mm.

[Association of prostasin gene rs12597511 polymorphism with outcomes of pregnancy with severe preeclampsia].

OBJECTIVE: To assess the association of prostasin gene rs12597511 polymorphism with clinical features and pregnancy outcomes among patients with severe preeclampsia. METHODS: Clinical manifestations, pregnancy outcomes and the genotypes of 179 patients with severe preeclampsia [early-onset group (≤34 gestational weeks): 79 cases; Late-onset group (>34 gestational weeks): 100 cases] and 222 normal-term pregnant women (control group) were collected. RESULTS: In the early-onset group, the patients with TC or CC genotype at rs12597511 had higher incidences of total complications, liver dysfunction, neonatal asphyxia, neonatal intracranial hemorrhage and perinatal mortality compared with those with TT genotype (P>0.05). Multiple logistic regression analysis showed that the complication rates of severe preeclampsia patients are closely related to TC or CC genotypes, 24 h urinary protein and gestational weeks of onset (OR=1.049, 95% CI:1.007-1.093, P=0.021; OR=1.031, 95% CI: 0.350-0.883, P=0.013; OR=0.733, 95% CI: 0.566-0.950, P=0.019), and the perinatal mortality is related to gestational weeks at delivery (OR=0.542, 95% CI: 0.331-0.887, P=0.015). CONCLUSION: Polymorphism of the prostasin gene is closely associated with poor pregnancy outcomes of early-onset severe preeclampsia.

Plumbagin induces ferroptosis in colon cancer cells by regulating p53-related SLC7A11 expression.

Objective: This study examined the mechanism through which plumbagin induces ferroptosis of colon cancer cells. Methods: CCK-8 assay was performed to examine the viability of colon cancer cells (SW480 and HCT116 cells) after they were treated with 0-, 5-, 10-, 15- and 20-µmol/L plumbagin. Colony formation assay and Transwell assay were used to examine the effects of 15-µmol/L plumbagin on the proliferation, invasive ability. The ferroptosis of SW480 and HCT116 cells and the expression of p-p53, p53 and SLC7A11 were analysed. The effects of blocking necrosis, apoptosis and ferroptosis on the anti-cancer effects of plumbagin were examined. After p53 was silenced, the effects of plumbagin on proliferation, invasion, ferroptosis and SLC7A11 expression were assessed. A tumour-bearing nude mouse model was used to examine the effects of p53 silencing and/or plumbagin on tumour growth, ferroptosis and SLC7A11 expression. Results: Plumbagin inhibited the proliferation of SW480 and HCT116 cells and their invasive and colony-forming abilities. It increased Fe2+ levels but significantly decreased GSH and GPX4 levels. When ferroptosis was inhibited, the effects of plumbagin on colon cancer cells were significantly alleviated. Plumbagin promoted the expression and phosphorylation of p53 and inhibited the mRNA and protein levels of SLC7A11. Silencing of p53 counteracted the effects of plumbagin on the ferroptosis and biological behaviour of SW480 and HCT116 cells. In mouse models of colon cancer, silencing of p53 attenuated the tumour-suppressing effects of plumbagin as well as its inhibitory effects on the protein level of SLC7A11 and restored the expression of GSH and GPX4. Conclusion: Plumbagin promotes ferroptosis and inhibits cell proliferation and invasion by decreasing the protein expression of SLC7A11 through p53.

Unveiling DNA damage repair-based molecular subtypes, tumor microenvironment and pharmacogenomic landscape in gastric cancer.

Objective: The current molecular classification system for gastric cancer covers genomic, molecular, and morphological characteristics. Non-etheless, classification of gastric cancer based upon DNA damage repair is still lacking. Here, we defined DNA damage repair-based subtypes across gastric cancer and identified clinicopathological, tumor microenvironment and pharmacogenomic features. Methods: Unsupervised clustering analysis was executed in the TCGA-STAD cohort based upon the transcriptional expression profiling of DNA damage repair genes. LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature. The identified subtypes or signature were externally verified in the GSE84426 or GSE84433 cohort. The transcriptional levels of immunomodulators, abundance of immune cells and somatic mutations were measured, respectively. Immunotherapeutic response, and drug sensitivity were investigated. The DNA damage repair-relevant genes were further experimentally verified. Results: Two DNA damage repair-based subtypes were identified, with the notable heterogeneity in prognostic stratification, tumor microenvironment and somatic mutations. The gene signature was generated for risk stratification and prognostic prediction, which was in relation to immunomodulators and immune cells. High-risk cases were more likely to respond to immunotherapy, with distinct pharmacogenomic landscapes between low- and high-risk groups. Higher levels of PAPPA2, MPO, MAGEA11, DEPP1, CPZ, and COLEC12 and lower level of CYTL1 were proven in gastric cancer cells versus controls. Silencing CYTL1 facilitated intracellular ROS accumulation and suppressed migration in gastric cancer cells. Conclusion: Collectively, the DNA damage repair-based classification is a suitable complement to existing molecular classification system, and the quantitative gene signature provides a robust tool in selecting specific therapeutic options.

Quantitative evaluation of anastomotic perfusion during colorectal surgery via indocyanine green fluorescence angiography: a narrative review.

Background and Objective: Quantitative studies of indocyanine green (ICG) are needed to optimize its evaluative potential in anastomotic perfusion during colorectal surgery. However, some limitations still existed in current studies about qualitative evaluations such as small-scale studies, the inconsistent concentration of the drug, the method of injection, etc. Therefore, this review summarized the primary quantitative parameters, image, method, and so on, during ICG fluorescence angiography aiming to further provide a theoretical basis for the application of ICG in laparoscopic colorectal surgery. Methods: The following keywords "indocyanine green or ICG", "anastomotic perfusion", and "colorectal surgery" were applied to search for literature published from 2002 to 2022 in the PubMed, Web of Science, and Medline databases. Then, the information about ICG fluorescence angiography in quantitative evaluation of anastomotic perfusion during colorectal surgery was summarized. Through integrating the experiences derived from the literature and our research center, the crucial quantitative parameters [such as T0, Tmax, Fmax, and S (Fmax/Tmax)], image characteristics, and standard operational process for ICG fluorescence angiography were summarized. Key Content and Findings: Firstly, quantitative parameters, including T0, Tmax, Fmax, and S (Fmax/Tmax) during the ICG fluorescence angiography could predict anastomotic leakage, and thus should be recorded. Secondly, the image curve generated by the software might differ among patients, which included a filling period, reducing period, and platform period; some patients even presented a second fluorescence intensity peak. Finally, present studies presented great heterogeneity regarding the injection dose of ICG, observation distance from the laparoscope to the anastomotic site, software, and so on, during ICG fluorescence angiography in quantitatively evaluating the intestinal blood perfusion. Conclusions: This review points out the challenges of ICG fluorescence angiography in quantitative evaluation of anastomotic perfusion and gives some advice. However, some difficulties and issues are non-neglectable during the clinical implications of the quantitative evaluation of ICG, such as standardizing the specific cut-off value about the quantitative parameters, injection dose of ICG, observation distance from the laparoscope to the anastomotic site, software, and so on, during ICG fluorescence angiography in quantitatively evaluating the intestinal blood perfusion to eliminate heterogeneity.

Long Noncoding RNA DLX6-AS1 Regulates the Growth and Aggressiveness of Colorectal Cancer Cells Via Mediating the miR-26a/EZH2 Axis.

Objective: To understand the regulation of long noncoding RNA DLX6-AS1-mediated miR-26a/EZH2 axis in the growth of colorectal cancer (CRC) cells. Methods: The expression of DLX6-AS1, miR-26a, and EZH2 was detected in CRC tissues by quantitative reverse transcription-polymerase chain reaction. The CRC HT-29 cell line was selected for transfection and subjected to observe the growth by MTT and colony formation assays, cell cycle by flow cytometry, and migration and invasion by wound healing and Transwell assays, respectively. Finally, the expression of cycle- and metastasis-related proteins was detected by Western blotting. Results: DLX6-AS1 and EZH2 were increased, with a decreased miR-26a in CRC tissues, showing significant negative correlations between DLX6-AS1 and miR-26a, and between miR-26a and EZH2. CRC patients at advanced stage or with lymphatic metastasis had higher DLX6-AS1 expression. Dual-luciferase reporter gene assay uncovered the targeting correlations between DLX6-AS1 and miR-26a, or miR-26a and EZH2. After transfection of DLX6-AS1 siRNA or EZH2 siRNA, the growth and metastasis of CRC cells were suppressed, arresting the cells in G0/G1 phase, with a magnificent reduction in the ratio of cells in S phase or G2/M phase; meanwhile, Cyclin D1, Vimentin, and MMP9 expressions decreased evidently, whereas E-cadherin expression was upregulated. Changes above were fully reversed after transfection of miR-26a inhibitor, whereas si-EZH2 transfection abolished the positive role of miR-26a inhibitor on growth of CRC cells. Conclusion: Silencing DLX6-AS1 may block the malignant features of CRC cells by inhibiting the expression of EZH2 through upregulation of miR-26a. Thus, it is critical to the development and progression of CRC.

A new frameshift mutation in L1CAM producing X-linked hydrocephalus.

BACKGROUND: X-linked hydrocephalus (XLH), characterized by mental retardation and bilateral adducted thumbs, often come out to be a genetic disorder of L1CAM. It codes the protein L1 cell adhesion molecule (L1CAM), playing a crucial role in the development of the nervous system. The objective of the study was to report a new disease-causing mutation site of L1CAM, and gain further insight into the pathophysiology of hydrocephalus. METHODS: We collect the samples of a couple and their second hydrocephalic fetus. Then, the whole-exome sequencing and in-depth mutation analysis were performed. RESULTS: The variant c.2491delG (p.V831fs), located in the exon 19 of L1CAM (chrX:153131214), could damage the L1CAM function by producing a frameshift in the translation of fibronectin type-III of L1CAM. CONCLUSION: We identified a novel disease-causing mutation in L1CAM for the first time, which further confirmed L1CAM as a gene underlying XLH cases.

Low-Temperature Methane Oxidation Triggered by Peroxide Radicals over Noble-Metal-Free MgO Catalyst.

Methane is a greenhouse gas that contributes to global warming. Hence, effectively removing the low concentration (<1000 ppm) of methane in the environment is an issue that deserves research in the field of catalysis. In this study, oxygen-magnesium bivacancies are simultaneously imbedded into MgO by designing an in situ reduction combustion atmosphere for oxygen release and substituting magnesium with carbon to induce the formation of magnesium vacancies. The DFT calculations reveal that the surface electron density of MgO is improved by the oxygen vacancy structure and the substitution of Mg by C in bulk; this accelerates migration of the charge from the material surface to the adsorbed oxygen species, which leads to abundant surface peroxide species that enable activation and oxidation of methane at a low temperature (below 200 °C). This work could provide a concept for developing non-noble or transition metal oxides for low-temperature activation and conversion of alkanes in the thermocatalytic field through reactive oxygen species.

Author Correction: Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.

In the original version of this Article, the Acknowledgements section omitted the National Key Research and Development Program of China (SQ2018YFC1003603).

Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.

Aberrant sperm flagella impair sperm motility and cause male infertility, yet the genes which have been identified in multiple morphological abnormalities of the flagella (MMAF) can only explain the pathogenic mechanisms of MMAF in a small number of cases. Here, we identify and functionally characterize homozygous loss-of-function mutations of QRICH2 in two infertile males with MMAF from two consanguineous families. Remarkably, Qrich2 knock-out (KO) male mice constructed by CRISPR-Cas9 technology present MMAF phenotypes and sterility. To elucidate the mechanisms of Qrich2 functioning in sperm flagellar formation, we perform proteomic analysis on the testes of KO and wild-type mice. Furthermore, in vitro experiments indicate that QRICH2 is involved in sperm flagellar development through stabilizing and enhancing the expression of proteins related to flagellar development. Our findings strongly suggest that the genetic mutations of human QRICH2 can lead to male infertility with MMAF and that QRICH2 is essential for sperm flagellar formation.

Soluble ST2, a preeclampsia-related cytokine receptor, is transported bi-directionally across the placenta.

INTRODUCTION: We aimed to elucidate whether soluble ST2 (sST2), a preeclampsia (PE)-related cytokine, in the maternal or fetal circulation could be transported to the other circulatory system across the placenta. METHODS: A placental perfusion model in a closed system was established and optimized. HPLC was performed to determine the dynamics of antipyrine levels in the perfusate. Placentas (n = 18) collected from healthy controls and PE patients were perfused without additional treatment or with added sST2 in the maternal or fetal circulation. The concentration of sST2 in the perfusate samples was quantified by ELISA. RESULTS: Monitoring of the antipyrine levels were used as a quality control and showed each placenta established successfully. In the untreated group, sST2 could be produced by the placenta and enter into both the maternal and fetal circulations, and significantly higher levels were detected in the maternal circulation. In placentas perfused with additional sST2 in the maternal circulation, a similar trend was observed as for the untreated placentas. When sST2 was added to the fetal circulation, increased sST2 was detected in the maternal circulation. Compared with the healthy controls, significantly elevated sST2 in the maternal side of PE patients were detected. CONCLUSION: Soluble ST2 could be bi-directionally transported across placentas. It was an active process that maintained a higher level of sST2 in the maternal circulation. Furthermore, the significant increase of sST2 in the maternal blood of PE patients was due to an impaired placental barrier as a result of PE.

Down-regulated long non-coding RNA-ATB in preeclampsia and its effect on suppressing migration, proliferation, and tube formation of trophoblast cells.

Preeclampsia is a pregnancy-specific syndrome and is one of the main causes of maternal, fetal, and neonatal morbidity and mortality. Inadequate trophoblast invasion and failure of uterine spiral artery remodeling exert a major role in the development of preeclampsia, especially the early-onset one. LncRNA-ATB is verified to be aberrantly expressed in many cancers and promote the invasion-metastasis and proliferation cascades. But little is known of lncRNA-ATB's role in preeclampsia. The aim of current study is to identify the changes of lncRNA-ATB in preeclampsia and its effects on trophoblast. The lncRNA-ATB levels were decreased in placental samples collected from preeclampsia women (n = 51) compared to those of healthy pregnant women (n = 40) by qRT-PCR analysis. Besides, it is demonstrated that lncRNA-ATB was intense stained in the trophoblast of the placenta by performing in-situ hybridization. By designing RNA interference species to suppress lncRNA-ATB and specific plasmids designed to overexpress lncRNA-ATB, we identify the role of lncRNA-ATB on the functions of trophoblast cell-line, HTR-8/SVneo. Inhibition of endogenous lncRNA-ATB decreased migration, proliferation, tube-formation of HTR-8/SVneo cells. In addition, overexpression of lncRNA-ATB promoted migration, proliferation, and tube-formation of HTR-8/SVneo cells. Therefore, lncRNA-ATB might be involved in the pathogenesis of preeclampsia by regulating the process of trophoblast invasion and endovascular formation.

Acute Fatty Liver of Pregnancy: A Retrospective Analysis of 56 Cases.

BACKGROUND: Acute fatty liver of pregnancy (AFLP) is a rare but life-threatening complication occurring in the third trimester. It is often fatal to both mother and fetus. The complicated clinical manifestations as well as an insufficient understanding of the disease make the precise diagnosis and effective treatment of AFLP challenging. A full understanding of the risk factors, clinical features, and test findings of AFLP is critical for its timely diagnosis and treatment. METHODS: We performed a retrospective study of 56 patients with AFLP between June 2008 and July 2013. We analyzed the clinical features, laboratory results, perioperative management, and patient outcomes. RESULTS: The initial symptoms varied considerably, with nausea and vomiting (13/56, 23%) being the most common. Liver-function indexes were remarkable, including elevated levels of serum alanine aminotransferase (262.16 ± 281.71 U/L), aspartate aminotransferase (260.98 ± 237.91 U/L), lactic dehydrogenase (1011.76 ± 530.34 U/L), and direct bilirubin (85.59 ± 90.02 µmol/L). Coagulation disorders were indicated by abnormal levels of fibrinogen (245.95 ± 186.11 mg/dL), D-dimer (2.46 ± 4.01 mg/L), and fibrin degradation products (43.62 ± 48.71 mg/L). The main maternal complications were hypoproteinemia (75%), coagulopathy (54%), and acute renal failure (39%). Multivariate logistic regression analysis identified prothrombin time (PT; odds ratio [OR] = 1.558, 95% confidence interval [CI] =1.248-1.946, PORCIP= 0.009) as risk factors. The perinatal infant death rate was related to gestational age at delivery (ORCI PORCI PORCI PConclusions: Nausea and vomiting may be the most common symptoms of AFLP. Indexes of liver dysfunction and coagulation disorders should also be considered. PT and INR are risk factors for fatal complications in patients with AFLP, and perinatal mortality is linked to the level of fibrin degradation products. Timely delivery is crucial to controlling the development of AFLP.

Associations of single nucleotide polymorphisms in miR-146a, miR-196a, miR-149 and miR-499 with colorectal cancer susceptibility.

BACKGROUND: MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25 nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes, as well as diverse human diseases including cancer. Recently, many studies investigated the association between SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: PubMed, EMBASE, CNKI databases were searched with the last search updated on November 5, 2013. For miR-196a2 rs11614913, a significantly decreased risk of CRC development was observed under three genetic models (dominant model: OR = 0.848, 95%CI: 0.735-0.979, P = 0.025; recessive model: OR = 0.838, 95%CI: 0.721-0.974, P = 0.021; homozygous model: OR = 0.754, 95%CI: 0.627-0.907, P = 0.003). In the subgroup analyses, miR-196a2*T variant was associated with a significantly decreased susceptibility of CRC (allele model: OR = 0.839, 95%CI: 0.749-0.940, P = 0.000; dominant model: OR = 0.770, 95%CI: 0.653-0.980, P = 0.002; recessive model: OR = 0.802, 95%CI: 0.685-0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570-0.847, P = 0.000). As for miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199, 95% CI 1.028-1.398, P = 0.021; heterozygous model: OR = 1.226, 95% CI 1.039-1.447, P = 0.013) demonstrated increased susceptibility to CRC. On subgroup analysis, significantly increased susceptibility of CRC was found in the genetic models (recessive model: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous model: OR = 1.202, 95% CI 1.013-1.425, P = 0.013) in the Asian group. CONCLUSIONS: These findings supported that the miR-196a2 rs11614913 and miR-149 rs2292832 polymorphisms may contribute to susceptibility to CRC.

Association between rs11614913 polymorphism in miR-196a2 and colorectal cancer risk: a meta-analysis.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs of 20-22 nucleotides in length, which regulate the translation or degradation of human messenger RNA (mRNA). MiRNAs involve in the regulation of most biological processes, as well as human diverse diseases including cancer. Recently, many studies investigated the association between miR-196a2 rs11614913 polymorphism and colorectal cancer (CRC), which showed inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 6 studies that included 1800 cases and 2329 controls. There was a statistically decreased risk of CRC in dominant model, recessive model and homozygous model. In the Asian group, significantly decreased susceptibility of CRC was found in allele model, dominant model, recessive model and homozygous model. As for the Caucasian group, none of genetic models demonstrates significant association between miR-196a2 rs11614913 polymorphism and susceptibility of CRC. CONCLUSIONS: These findings supported that miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of CRC.