Fabrication and evaluation of porous coatings doped with bioactive elements on titanium surfaces.

OBJECTIVE: Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification. MATERIALS AND METHODS: Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments. RESULTS: A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs. CONCLUSIONS: A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity.

[Perioperative management of non-thyroid surgery in patients with thyroid dysfunction].

Thyroid diseases are relatively common in clinical practice. Surgery and use of related drugs may exacerbate the underlying thyroid diseases, increasing the difficulty of perioperative management. However, there is a lack of guidelines and consensus for non-thyroid surgery in patients with thyroid dysfunction. This review mainly summaries the perioperative management of non-thyroid surgery in patients with hypothyroidism and hyperthyroidism to provide clinical treatment suggestions and reduce the risk of perioperative complications.

Beneficial Effects of High-Intensity Interval Training and Dietary Changes Intervention on Hepatic Fat Accumulation in HFD-Induced Obese Rats.

Lifestyle intervention encompassing nutrition and physical activity are effective strategies to prevent progressive lipid deposition in the liver. This study aimed to explore the effect of dietary change, and/or high-intensity interval training (HIIT) on hepatic lipid accumulation in high fat diet (HFD)-induced obese rats. We divided lean rats into lean control (LC) or HIIT groups (LH), and obese rats into obese normal chow diet (ND) control (ONC) or HIIT groups (ONH) and obese HFD control (OHC) or HIIT groups (OHH). We found that dietary or HIIT intervention significantly decreased body weight and the risk of dyslipidemia, prevented hepatic lipid accumulation. HIIT significantly improved mitochondrial fatty acid oxidation through upregulating mitochondrial enzyme activities, mitochondrial function and AMPK/PPARalpha/CPT1alpha pathway, as well as inhibiting hepatic de novo lipogenesis in obese HFD rats. These findings indicate that dietary alone or HIIT intervention powerfully improve intrahepatic storage of fat in diet induced obese rats. Keywords: Obesity, Exercise, Diet, Mitochondrial function, Lipid deposition.

Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese population.

BACKGROUND: Breast cancer brain metastasis (BCBM) is a crucial issue in the treatment of breast cancer and is associated with poor prognosis. Therefore, novel therapeutic targets are urgently needed in clinical practice. In this study, we aimed to identify potential actionable targets in brain metastases (BMs) utilising the FoundationOne® CDx (F1CDx). PATIENTS AND METHODS: Formalin-fixed paraffin-embedded archived specimens including 16 primary breast tumours (PTs), 49 BCBMs and 7 extracranial metastases (ECMs) from 54 patients who underwent surgery for BCBM were tested using F1CDx. Tumour-infiltrated lymphocytes (TILs) of BMs were also tested using haematoxylin-eosin staining. RESULTS: The median tumour mutational burden (TMB) and TILs in BMs were 5.0 (range 0-29) mut/Mb and 1.0% (range 0%-5.0%), respectively. High TMB (≥10 mut/Mb) was detected in four cases (8%). Genomic alterations (GAs) were detected in all samples. The top-ranked somatic mutations in BMs were TP53 (82%), PIK3CA (35%), MLL2 (22%), BRCA2 (14%) and ATM (14%) and the most prevalent copy number alterations were ERBB2 (64%), RAD21 (36%), CCND1 (32%), FGF19 (30%) and FGF3 (30%). The most prevalent GAs were relatively consistent between paired PTs and BMs. Actionable GAs were detected in 94% of all BMs. Consistent rate in actionable GAs was 38% (6/16) between paired PTs/ECMs and BMs. Compared to matched PTs/ECMs, additional actionable GAs (BRAF, FGFR1, PTEN, KIT and CCND1) were discovered in 31% (5/16) of the BMs. CONCLUSIONS: TMB and TILs were relatively low in BCBMs. Comparable consistency in actionable GAs was identified between BCBMs and matched PTs/ECMs. It was, therefore, logical to carry out genomic testing for BCBMs to identify potential new therapeutic targets when BCBM specimens were available, as ∼31% of samples carried additional actionable GAs.

[The detecting value of virtual non-calcium technique of dual-energy CT for bone marrow edema around nontraumatic osteonecrosis of the femoral head].

Objective: To evaluate the value of virtual non-calcium (VNCa) technique of dual-energy CT (DECT) for detecting bone marrow edema (BME) around nontraumatic osteonecrosis of the femoral head (ONFH) using MRI as reference standard. Methods: Nontraumatic ONFH patients were prospectively studied in the Fourth Medical Center of Chinese PLA General Hospital from October 2022 to May 2023, and their MRI and DECT images were analyzed. The diagnostic efficiency of the subjective assessment of BME around ONFH by two radiologists in VNCa color-coded images were calculated using the MRI results as the reference standard. The BME ranges were compared between VNCa images and MRI. Traditional CT values and VNCa CT values were compared between normal bone marrow and BME. The receiver operator characteristic (ROC) curve was established based on the statistically different CT values, and the area under the curve (AUC) was calculated to find the threshold to distinguish normal bone marrow from BME and evaluate the diagnostic efficacy. Results: Thirty patients with ONFH were included, including 24 males and 6 females, aged (39±12) years. There were 18 bilateral hips and 12 unilateral hips, with a total of 48 hips, 34 hips of which showed BME on MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of subjective detection of BME on VNCa color coded maps by two physicians were 97.1% (33/34) and 97.1% (33/34), 92.9% (13/14) and 71.4% (10/14), 97.1% (33/34) and 89.2% (33/37), 92.9% (13/14) and 90.9% (10/11), 95.8% (46/48) and 89.6% (43/48), respectively, with no statistical difference (all P>0.05).There was no statistical difference between VNCa color-coded images and MRI in the BME range (P=1.160). The traditional CT values measured by the two radiologists were in good agreement with VNCa CT values, with intraclass correlation coefficient (ICC) of 0.948 (95%CI: 0.908-0.971) and 0.982 (95%CI: 0.969-0.990), respectively. The traditional CT value of normal bone marrow was (400.7±82.8) HU, and that of BME was (443.7±65.7) HU, with no statistical difference (P=0.062). The VNCa CT value of normal bone marrow was (-103.1±27.8) HU, and that of BME was (-32.9±25.7) HU, with statistical difference (P<0.001). The AUC of distinguishing normal bone marrow from BME based on VNCa CT value was 0.958 (95%CI: 0.857-0.995). The best cut-off value was -74.5 HU, and when the VNCa CT value was higher than -74.5 HU, the sensitivity, specificity, PPV, NPV and accuracy of diagnosing BME were 97.1%, 92.9%, 97.1%, 92.9% and 95.8 %, respectively. Conclusion: The VNCa technique of DECT has high efficiency in detecting BME around ONFH, and can accurately demonstrate the range of BME.

Determinants of depressive symptoms at individual, school and province levels: a national survey of 398,520 Chinese children and adolescents.

OBJECTIVES: The aims of this study were to describe the national distribution of depressive symptoms in Chinese children and adolescents, to examine the determinants of depressive symptoms at individual, school and province levels and to assess the gender and age differences in the effect of school factors on depressive symptoms. STUDY DESIGN: This was a national cross-sectional study. METHODS: A school-based online survey was conducted in mainland China from between December 1, 2021, and January 1, 2022. A total of 398,520 eligible participants were included in the analysis. School-level data were drawn from students, headteachers and Baidu Maps, and province-level data were obtained from the national human development report. The Patient Health Questionnaire-2 was used to measure depressive symptoms. RESULTS: Areas with the highest mean scores for depressive symptoms were in the northeastern, inner central and southwestern regions of China. At the individual level, younger age, male sex, being an only child, Han ethnicity, lower body mass index, more days of exercise, less drinking and smoking behaviours, higher subjective family socio-economic status (SES) and popularity in school were related to fewer depressive symptoms; however, objective family SES and maternal education were not related to fewer depressive symptoms. The school-level variables of public status, psychological activities and psychological courses and province-level variable of higher Human Development Index were associated with fewer depressive symptoms. The effect of psychological courses and activities on depressive symptoms was greater in females. CONCLUSIONS: The results showed multilevel factors related to depressive symptoms and emphasised the importance of implementing school-based psychological activities to ameliorate depressive symptoms in Chinese children and adolescents across age and gender.

[Effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022].

OBJECTIVE: To evaluate the effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, so as to provide insights into echinococcosis control. METHODS: Administrative villages were sampled using a multi-stage cluster random sampling method from Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, and all residents at ages of 12 years and older in the sampled villages were screened for echinococcosis, and schools were sampled using a cluster sampling method, and all children at ages of 12 years and older in the sampled schools were screened for echinococcosis. Domestic dogs were sampled using a systematic random sampling method, and one domestic dog stool sample was collected from each household. Stray dog stool samples were collected outside the villages, and Echinococcus coproantigens were detected using enzyme-linked immunosorbent assay in domestic and stray dogs. In addition, echinococcosis was screened in sheep and cattle in designated slaughterhouses in Tianzhu Tibetan Autonomous County. The trends in the prevalence of echinococcosis in humans and livestock and the positive rate of Echinococcus coproantigens in dogs were examined with the Cochran-Armitage trend test. In addition, individuals screened for echinococcosis were randomly sampled from 2007 to 2022 for survey on the awareness of echinococcosis control knowledge. RESULTS: A total of 290 356 person-times were screened for echinococcosis among residents at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 094 residents detected with cystic echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 358.602, P < 0.001). A total of 32 931 person-times were screened for echinococcosis among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 296 children detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 267.673, P < 0.001). A total of 33 230 domestic dog stool samples were tested for Echinococcus coproantigens in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 777 Echinococcus coproantigens-positive samples tested, and the positive rate of Echinococcus coproantigens appeared a tendency towards a decline in domestic dogs over years (χ2 = 2 210.428, P < 0.001), while the positive rate of Echinococcus coproantigens showed a tendency towards a rise in domestic animals from 2016 to 2022 (χ2 = 37.745, P < 0.001). The positive rate of Echinococcus coproantigens remained relatively stable in stray dogs in Tianzhu Tibetan Autonomous County, Gansu Province from 2019 to 2022 (χ2 = 0.315, P = 0.575). A total of 10 973 sheep were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2007 to 2022, with 334 sheep detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a decline in sheep over years (χ2 = 53.579, P < 0.001); however, there was no significant change in the detection of echinococcosis during the period from 2015 through 2022 (χ2 = 1.520, P = 0.218). A total of 2 400 cattle were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2017 to 2022, with 231 cattle detected with echinococcosis, and the detection of echinococcosis showed a tendency towards a decline over years (χ2 = 5.579, P < 0.05). The awareness of echinococcosis control knowledge increased from 44.37% in 2007 to 94.00% in 2022 among residents at ages of 12 years and older and from 52.50% in 2007 to 92.50% in 2022 among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, respectively. CONCLUSIONS: There has been a reduction in the detection of echinococcosis in humans and domestic animals and the positive rate of Echinococcus coproantigens in dogs and a rise in the awareness of the echinococcosis control knowledge following the implementation of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province; however, integrated echinococcosis control measures are still required for further control of the prevalence of echinococcosis.

[Effect of TRPM8 on pain symptom and neuronal proliferation in mice with interstitial cystitis/bladder pain syndrome].

Objective: To explore the effects between transient receptor potential melastatin 8 (TRPM8) on pain symptom and neuronal proliferation in mice with interstitial cystitis/bladder pain syndrome (IC/BPS). Methods: Female wild-type C57BL/6 mice (8-10 weeks old) were divided into control group, IC/BPS model group, and IC/BPS model+menthol group (6 mice each) by random number table method; TRPM8 knockout mice were randomly divided into TRPM8 knockout group and TRPM8 knockout model group (6 mice each). The IC/BPS model group, the IC/BPS model+menthol group, and the TRPM8 knockout model group were injected subcutaneously with residues 65-84 of murine uroplakin 3A (UPK3A65-84). The IC/BPS model+menthol group continued to be injected with menthol. After successful modeling, the differences in pain thresholds between the groups were assessed by mechanosensitivity. The bladder wall was injected with a cell membrane red fluorescent probe (Dil), and the dorsal root ganglion (DRG) tissues were collected 10 days later. The differences in the protein and mRNA levels of TRPM8 and GAP43 in the groups were detected by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Immunofluorescence was used to detect the distribution of TRPM8 expression with GAP43 or Dil in DRG tissues. The relationship between TRPM8 and pain symptom and its role in neuronal proliferation in IC/BPS mice were analyzed. Results: The models were all constructed successfully. Compared with the control group, the pain thresholds of mice in the IC/BPS model group and IC/BPS model+menthol group were reduced [(8.50±1.22), (5.50±1.05) vs (11.67±2.16), respectively, all P<0.001]. Compared with the control group, the expression of TRPM8 mRNA was elevated in the IC/BPS model group and IC/BPS model+menthol group, while TRPM8 was not expressed in the TRPM8 knockout group [(3.16±0.05), (6.46±0.21), and 0 vs (1.00±0.06), respectively, all P<0.001]. The expression of TRPM8 protein and mRNA in each group had the same trend (P<0.001). Compared with the control group, the expression of GAP43 mRNA in the DRG of the IC/BPS model group and the IC/BPS model+menthol group was increased, whereas the expression of GAP43 mRNA in the TRPM8 knockout model group was decreased (all P<0.001). The trend of GAP43 protein expression was the same as that of mRNA expression (P<0.001). Immunofluorescence results showed an increase in the number of GAP43-positive neurons in the DRG of the IC/BPS model group and the IC/BPS model+menthol group, and a decrease in the TRPM8 knockout group compared with the control group (all P<0.001). Compared with the control group, the number of Dil-positive neurons in the DRG of the IC/BPS model group and the IC/BPS model+menthol group was increased, while the TRPM8 knockout group was decreased (all P<0.001). Conclusion: TRPM8 can exacerbate pain symptom in IC/BPS mice, and the mechanism may be related to the induction of sensory nerve proliferation at the DRG level.

Neutron-gamma discrimination with broaden the lower limit of energy threshold using BP neural network.

Neutron-gamma discrimination is a tough and significative in experimental neutrons measurements procedure, especially for low-energy neutrons signal discrimination. In this work, based on the Pulse Shape Discrimination (PSD) and Back-Propagation (BP) artificial neural networks, a neutron-gamma discrimination method is developed to broaden the lower limit of energy threshold with the hidden layer of 20 neurons. Compared with neutron-gamma discrimination method based on PSD only, the developed neutron-gamma discrimination method based on the PSD and BP-ANN can discriminate neutron and gamma-ray signals with low energy threshold, which can discriminate signals up to 99.93%. Moreover, this work can reduce the energy threshold from 350 keV to 70 keV, as well as the acquired data utilization increased from 60% to more than 99.9%, which overcome the hardware limitations and distinguish neutron and gamma-ray signals, effectively. The developed neutron-gamma discrimination method and the trained neural network can be directly used to other experimental neutrons measurements.

[Transperineal targeted prostate puncture combined with rapid pathological examination in the diagnosis of prostate cancer].

Exploring the clinical value of multiparametric magnetic resonance (Mp-MRI)-cognitive fusion method of targeted transperineal prostate puncture combined with rapid pathological diagnosis. Patients with suspected prostate cancer admitted to our hospital from 2022.01 to 2023.05 were selected as the study subjects, and Mp-MRI was performed and the suspected lesions were scored by the Prostate Imaging Reporting and Data System (PI-RADS). The enrolled patients were randomly divided into the transperineal prostate targeted puncture plus rapid pathology group (experimental group) and the transperineal prostate systematic combined targeted puncture plus conventional pathology group (control group), and the positive puncture rate, pathological findings, and complications were analyzed to compare the differences between the two groups. A total of 100 patients were enrolled, 53 in the experimental group [age 55-89 years, (73.17±7.79) years; tPSA 7.01-100 µg/L, mean 21.34 (12.38, 44.42) µg/L]and 47 in the control group [age 60-87 years, (71.96±7.07) years; tPSA 6.11-98.82 µg/L, mean 18.77 (9.04, 38.09) µg/L], and there was no significant difference between the two groups in the diagnostic positivity rate of overall PCa and clinically significant PCa (P>0.05); there was no significant difference in the highest Gleason score of pathological tissues between the two groups (P>0.05); the number of cases of medically induced sarcoid hematuria in the experimental group were significantly reduced compared with the control group (P<0.05). In terms of biopsy pain score (VAS), patients in the experimental group experienced less pain than those in the control group (P<0.05). The Mp-MRI-cognitive fusion method of transperineal targeted prostate puncture combined with rapid frozen section pathological examination can provide rapid and accurate pathological results, reduce the chance of post-puncture complications, and alleviate the pain caused by puncture sampling, which has high clinical value.

[A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey].

Objective: To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors. Methods: From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions. Results: Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects (χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients (χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications (χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment (R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not (OR=1.83, P<0.001). Conclusions: Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Intestinal Translocation of Live Porphyromonas gingivalis Drives Insulin Resistance.

Periodontitis has been emphasized as a risk factor of insulin resistance-related systemic diseases. Accumulating evidence has suggested a possible "oral-gut axis" linking oral infection and extraoral diseases, but it remains unclear whether periodontal pathogens can survive the barriers of the digestive tract and how they play their pathogenic roles. The present study established a periodontitis mouse model through oral ligature plus Porphyromonas gingivalis inoculation and demonstrated that periodontitis aggravated diet-induced obesity and insulin resistance, while also causing P. gingivalis enrichment in the intestine. Metabolic labeling strategy validated that P. gingivalis could translocate to the gastrointestinal tract in a viable state. Oral administration of living P. gingivalis elicited insulin resistance, while administration of pasteurized P. gingivalis had no such effect. Combination analysis of metagenome sequencing and nontargeted metabolomics suggested that the tryptophan metabolism pathway, specifically indole and its derivatives, was involved in the pathogenesis of insulin resistance caused by oral administration of living P. gingivalis. Moreover, liquid chromatography-high-resolution mass spectrometry analysis confirmed that the aryl hydrocarbon receptor (AhR) ligands, mainly indole acetic acid, tryptamine, and indole-3-aldehyde, were reduced in diet-induced obese mice with periodontitis, leading to inactivation of AhR signaling. Supplementation with Ficz (6-formylindolo (3,2-b) carbazole), an AhR agonist, alleviated periodontitis-associated insulin resistance, in which the restoration of gut barrier function might play an important role. Collectively, these findings reveal that the oral-gut translocation of viable P. gingivalis works as a fuel linking periodontitis and insulin resistance, in which reduction of AhR ligands and inactivation of AhR signaling are involved. This study provides novel insight into the role of the oral-gut axis in the pathogenesis of periodontitis-associated comorbidities.

An immunogenomic exome landscape of triple positive primary antiphospholipid patients.

Primary antiphospholipid syndrome is characterized by thrombosis and autoantibodies directed against phospholipids or associated proteins. The genetic etiology of PAPS remains unknown. We enrolled 21 patients with thromboembolic events associated to lupus anticoagulant, anticardiolipin and anti ß2 glycoprotein1 autoantibodies. We performed whole exome sequencing and a systematic variant-based analysis in genes associated with thrombosis, in candidate genes previously associated with APS or inborn errors of immunity. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. Variants were identified following a state-of-the-art pipeline. Enrichment analysis was performed by comparing with the control cohort. We found an absence of significant HLA bias and genetic heterogeneity in these patients, including when testing combinations of rare variants in genes encoding for proteins involved in thrombosis and of variants in genes linked with inborn errors of immunity. These results provide evidence of genetic heterogeneity in PAPS, even in a homogenous series of triple positive patients. At the individual scale, a combination of variants may participate to the breakdown of B cell tolerance and to the vessel damage.

[Clinical effect of modified vertical rectus abdominis myocutaneous flap in repairing skin and soft tissue defects after abdominoperineal resection for rectal cancer].

Objective: To investigate the clinical effect of the modified vertical rectus abdominis myocutaneous flap in repairing the skin and soft tissue defect after abdominoperineal resection for rectal cancer. Methods: This study was a retrospective observational study. From June 2019 to July 2022, five male patients with low rectal cancer who were conformed to the inclusion criteria were admitted to the Department of Basic Surgery of Xiangya Hospital of Central South University, with ages ranging from 65 to 70 years and the sizes of the perianal skin ulcers ranging from 5 cm×4 cm to 11 cm×9 cm, and all of them underwent abdominoperineal resection. The secondary skin and soft tissue defects in the perineum with an area of 8 cm×6 cm-14 cm×12 cm (with the depth of pelvic floor dead space being 10-15 cm) were repaired intraoperatively with transplantation of modified vertical rectus abdominis myocutaneous flaps with the skin area being 9 cm×7 cm-16 cm×12 cm, the volume of the muscle being 18 cm×10 cm×5 cm-20 cm×12 cm×5 cm, and the vessel pedicle being 18-20 cm in length. During the operation, most of the anterior sheath of the rectus abdominis muscle was retained, the flap was transferred to the recipient area through the abdominal cavity, the remaining anterior sheaths of the rectus abdominis muscle on both sides of the donor area were repeatedly folded and sutured, the free edge of the transverse fascia of the abdomen was sutured with the anterior sheath of the rectus abdominis muscle, and the donor area skin was directly sutured. After the operation, the survival of the transplanted myocutaneous flap was observed. The occurrence of complications in the perineal recipient area was recorded within 2 weeks after the operation. The recovery of the perineal recipient area and the abdominal donor area was observed during follow-up, and the occurrence of complications in the donor area of the abdomen as well as the recurrence of tumors and metastasis were recorded. Results: All transplanted myocutaneous flaps in 5 patients survived after surgery. One patient had dehiscence of the incision in the perineal recipient area 2 days after surgery, which healed after 7 d with intermittent dressing changes and routine vacuum sealing drainage treatment. In the other 4 patients, no complications such as incisional rupture, incisional infection, or fat liquefaction occurred in the perineal recipient area within 2 weeks after surgery. Follow-up for 6-12 months after discharge showed that the skin of the perineal recipient area had good color, texture, and elasticity, and was not bloated in appearance; linear scars were left in the perineal recipient area and the abdominal donor area without obvious scar hyperplasia or hyperpigmentation; no complications such as incisional rupture, incisional infection, intestinal adhesion, intestinal obstruction, or weakening of the abdominal wall strength occurred in the abdominal donor area, and the abdominal appearance was good with no localized bulge or formation of abdominal hernia; there was no local recurrence of tumor or metastasis in any patient. Conclusions: The surgical approach of using the modified vertical rectus abdominis myocutaneous flap to repair the skin and soft tissue defects after abdominoperineal resection for rectal cancer is relatively simple in operation, can achieve good postoperative appearances of the donor and recipient areas with few complications, and is worthy of clinical promotion.

Epigenetic Regulation of Ameloblast Differentiation by HMGN Proteins.

Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast differentiation are not fully understood. Here we show that the high mobility group N (HMGN) nucleosomal binding proteins modulate the rate of ameloblast differentiation and enamel formation. We found that HMGN1 and HMGN2 proteins are downregulated during mouse ameloblast differentiation. Genetically altered mice lacking HMGN1 and HMGN2 proteins show faster ameloblast differentiation and a higher rate of enamel deposition in mice molars and incisors. In vitro differentiation of induced pluripotent stem cells to dental epithelium cells showed that HMGN proteins modulate the expression and chromatin accessibility of ameloblast-specific genes and affect the binding of transcription factors epiprofin and PITX2 to ameloblast-specific genes. Our results suggest that HMGN proteins regulate ameloblast differentiation and enamel mineralization by modulating lineage-specific chromatin accessibility and transcription factor binding to ameloblast regulatory sites.

Polymicrobial Infection Induces Adipose Tissue Dysfunction via Gingival Extracellular Vesicles.

Recent studies have indicated that periodontitis promotes metabolic dysregulation and insulin resistance by affecting the function of white adipose tissue (WAT). However, the mechanisms linking periodontitis to adipose tissue dysfunction still need to be explored. Extracellular vesicles (EVs) deliver messages to distal sites and regulate their function. Also, recent studies have shown that periodontitis changes the composition of EVs in body fluids and that EVs might be one of the mechanisms underlying the relationship between periodontitis and insulin resistance. Herein, we explored the impact of polymicrobial oral infection with periodontal pathogens on the function of WAT and the role of gingival EVs (gEVs) in the process. Mice were subjected to oral inoculation with 109 Porphyromonas gingivalis and 108 Fusobacterium nucleatum every other day for 14 wk. This prolonged bacterial infection induced WAT dysfunction, characterized by reduced levels of AKT phosphorylation, adiponectin, leptin, and genes associated with adipogenesis and lipogenesis. We successfully isolated gEVs with satisfactory yield and purity. The RNA sequencing results showed that the differentially expressed microRNAs in the gEVs of mice with polymicrobial oral infection were involved in insulin signaling and adipose tissue function. Notably, our in vitro experiments and RNA sequencing results revealed the functional similarities between gEVs and plasma-derived EVs. Furthermore, intraperitoneal injection with gEVs derived from mice with oral infection induced the dysfunction of WAT in healthy mice. Overall, our findings provide evidence for the influence of polymicrobial oral infection on WAT function and propose gEVs as a novel pathway through which periodontal infection may exert its effects on WAT.

[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.