Comparative clinical study of the modified Broström procedure for the treatment of the anterior talofibular ligament injury-outcomes of the open technique compared to the arthroscopic procedure.

PURPOSE: To observe the clinical efficacy and safety of arthroscopic-modified Broström surgery for the treatment of anterior talofibular ligament injury. METHODS: The clinical data of 51 cases with anterior talofibular ligament injury were retrospectively analyzed, in which 23 patients were treated by arthroscopic-modified Broström surgery (arthroscopic surgery group) and 28 patients were treated by open-modified Broström surgery (open surgery group). The time to surgery, hospital stay, visual analog scale (VAS) scores of ankle pain, American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot scores, and incidence rate of complications were compared between the two groups. RESULTS: (1) General results: compared with open surgery group, arthroscopic surgery group had shorter time to surgery and hospital stay ((33.8 ± 6.7) min, (42.1 ± 8.5) min, t = 1.468, P = 0.001; (2.2 ± 1.4) d, (5.8 ± 1.6) d, t = 1.975, P = 1.975, P = 0.002). (2) VAS scores of ankle pain: there was an interaction effect between the time and group factors (F = 0.378, P = 0.018); overall, there was no statistically significant difference in VAS scores of ankle pain between the two groups, i.e., there was no grouping effect (F = 1.865, P = 0.163); there was statistically significant difference in VAS score of ankle pain at different time points before and after operation, i.e., there was a time effect (F = 1.675, P = 0.000); the VAS scores of ankle pain showed a decreasing trend with time in both groups, but the decreasing trend was not completely consistent between the two groups ((7.78 ± 1.23), (1.23 ± 1.24), (1.03 ± 0.35), (1.01 ± 0.28), F = 0.568, P = 0.000. (7.45 ± 1.43), (1.45 ± 1.87), (1.23 ± 0.55), (1.04 ± 0.37), F = 1.358, P = 0.000); there was no statistically significant difference in VAS score of ankle joint pain between the two groups six and 12 months before and after surgery (t = 2.987, P = 0.055; t = 1.654, P = 2.542; t = 0.015, P = 0.078); the VAS scores of ankle pain in the arthroscopic surgery group was lower than that in the open surgery group three months after operation (t = 1.267, P = 0.023). (3) AOFAS ankle and hindfoot scores: there was an interaction effect between time and grouping factors (F = 2.693, P = 0.027); overall, there was no statistically significant difference in the AOFAS ankle and hindfoot scores between the two groups, i.e., there was no grouping effect (F = 1.983, P = 0.106); there was statistically significant difference in the AOFAS ankle and hindfoot scores at different time points before and after surgery, i.e., there was a time effect (F = 34.623, P = 0.000); the AOFAS ankle and hindfoot scores of the two groups showed an increasing trend with time, but the increasing trend of the two groups was not completely consistent ((48.19 ± 12.89), (89.20 ± 8.96), (90.24 ± 7.89), (91.34 ± 9.67), F = 25.623, P = 0.000; (49.35 ± 13.28), (86.78 ± 12.34), (88.78 ± 9.78),(91.43 ± 7.98), F = 33.275, P = 0.000); there was no statistically significant difference in the AOFAS ankle and hindfoot scores between the two groups 12 months before/after surgery (t = 2.145，P = 0.056；t = 2.879，P = 0.389); compared with open surgery group, the arthroscopic surgery group had higher AOFAS ankle and hindfoot scores 3/6 months after surgery (t = 1.346, P = 0.014; t = 1.874, P = 0.028). CONCLUSION: For the treatment of anterior talofibular ligament injury, arthroscopic surgery group is superior to open surgery group in ankle pain relief and functional recovery and has shorter operation time and hospital stay compared with open surgery group.

Analysis of Risk Factors for in-hospital Death in Elderly Patients with TEXAS Stage 3 and 4 Diabetic Foot Ulcers after Tibial Transverse Translation: A Case-Control Study.

OBJECTIVE: Chinese physicians developed the Tibial Transverse Transport (TTT) technique to treat diabetic foot ulcers with more than 90% effective rate. But this method still could not avoid the in-hospital death of patients. This study adopted a case-control study to explore the risk factors of in-hospital death in elderly patients with chronic ischemic diabetic foot after receiving TTT treatment. METHODS: A total of 54 patients were included in the study from January 1, 2017 to April 30, 2021, by being paired with the cases in case group with their demographic data and results of blood routine, liver and kidney function. There were nine patients in case group with six male and three male. Forty-five patients were selected in control group according to gender and diabetes type with 30 male and 15 female. Single factor logics regression analysis was used to explore the risk factors and odd ratios (OR) of in-hospital death in patients. The nomogram and decision curve analysis (DCA) had been done by R Studio software. RESULTS: The study found that age, course of diabetic foot, small dense low-density Lipoprotein (smLDL), homocysteine (Hcy), superoxide dismutase (SOD), and prealbumin (PA) were risk factors for in-hospital death of patients. The smLDL had the highest risk. The nomogram showed that PA accounted for the largest proportion in the death risk factors. The results of DCA proved that above six risk factors were the risk factors for patients with TEXAS Stage 3 and 4 diabetic foot ulcers. CONCLUSION: In the future diagnosis and TTT treatment for diabetic foot ulcers, doctors need to pay close attention to age, course of diabetic foot, smLDL, Hcy, SOD, and PA.

[The role of bronchoscopy in slide tracheoplasty in children]. / 支气管镜在儿童Slide气管成形术中的应用.

OBJECTIVES: To study the role of bronchoscopy in slide tracheoplasty. METHODS: A retrospective analysis was conducted on the diagnosis and treatment of four children with tracheal stenosis admitted to Hunan Provincial People's Hospital from 2017 to 2020. The role of bronchoscopy was summarized in the preoperative evaluation, intraoperative positioning and measurement, and postoperative wound evaluation and treatment during slide tracheoplasty. RESULTS: Bronchoscopy evaluation before slide tracheoplasty showed that 3 of the 4 children had complete trachea rings, 2 had pulmonary artery sling, and 2 had multiple stenosis. Slide tracheoplasty was performed in the hospital on 3 children, and the midpoint of the stenosis segment was judged under bronchoscopy, and the length of the stenosis segment was measured, which assisted in the resection of the stenosis segment of the trachea. The pathogens were identified by lavage after the surgery. One child who developed scar traction 9 months after slide tracheoplasty in another hospital was improved by interventional treatment under bronchoscopy. Mucosal changes were found under bronchoscopy in 2 children 4 days after surgery, and the treatment plan was adjusted. One month after surgery, 2 children had granulation hyperplasia, which was improved by cryotherapy under bronchoscopy. One child abandoned treatment due to anastomotic necrosis and died. Three survivors were followed up for over 6 months with good prognosis, but all had tracheobronchial malacia. CONCLUSIONS: Bronchoscopy can be used for the management of slide tracheoplasty in children with tracheal stenosis, which is helpful to postoperative rehabilitation and follow-up.

Construction and analysis of a nomogram prediction model for post-infectious bronchiolitis obliterans in children with adenovirus pneumonia after invasive mechanical ventilation.

BACKGROUND: Post-infectious bronchiolitis obliterans (PIBO) is the most common sequelae in children with adenovirus pneumonia (ADVP). However, there are few studies on the risk factors for PIBO occurrence. This study aims to investigate the risk factors for PIBO in pediatric patients with severe ADVP, especially after invasive mechanical ventilation (IMV), as well as to build a nomogram prediction model. METHODS: The clinical data, laboratory and imaging features, and treatment of 863 children with ADVP under 3 years old who were admitted to our hospital from January to December 2019 were retrospectively analyzed. Among them, 66 children with severe ADVP received IMV treatment. The situation and the influencing factors of PIBO in children with severe ADVP were explored, and a nomogram prediction model was constructed. RESULTS: Among the 863 cases of ADVP, 46 cases (5.33%) developed PIBO. Duration of fever, IMV, complications, and neutrophil percentage were independent risk factors for PIBO in children with ADVP. Among the 66 patients with ADVP who underwent IMV, 33 patients (50.0%) developed PIBO. Gender, duration of fever, adenovirus (ADV) load, and mixed fungal coinfections were independent risk factors for PIBO. In the nomogram prediction model analysis, the area under the curve (AUC) was 0.857; in addition, Hosmer‒Lemeshow (H-L) detection reflected good alignment (χ2 = 68.75, P < 0.01). CONCLUSIONS: A nomogram prediction model, which can be utilized to predict PIBO occurrence in pediatric patients with ADVP after IMV at an early time period, was successfully built.

Preconception paternal mental disorders and child health: Mechanisms and interventions.

Mental illness is a significant global health issue with a steady prevalence. High heritability is suspected, but genome-wide association studies only identified a small number of risk genes associated with mental disorders. This 'missing inheritance' can be partially explained by epigenetic heredity. Evidence from numerous animal models and human studies supports the possibility that preconception paternal mental health influences their offspring's mental health via nongenetic means. Here, we review two potential pathways, including sperm epigenetics and seminal plasma components. The current review highlights the role of sperm epigenetics and explores epigenetic message origination and susceptibility to chronic stress. Meanwhile, possible spatiotemporal windows and events that induce sexually dimorphic modes and effects of paternal stress transmission are inferred in this review. Additionally, we discuss emerging interventions that could potentially block the intergenerational transmission of paternal psychiatric disorders and reduce the incidence of mental illness. Understanding the underlying mechanisms by which preconception paternal stress impacts offspring health is critical for identifying strategies supporting healthy development and successfully controlling the prevalence of mental illness.

Effect of tibial cortex transverse transport in patients with recalcitrant diabetic foot ulcers: A prospective multicenter cohort study.

Background: Management of recalcitrant diabetic foot ulcer (DFU) remains difficult. Distraction osteogenesis mediates new bone formation and angiogenesis in the bone itself and the surrounding tissues. Recently it was reported that tibial cortex transverse transport (TTT) was associated with neovascularization and increased perfusion at the foot in patients with recalcitrant DFUs and facilitated healing and limb salvage. However, the findings were from several single-center studies with relatively small populations, which need to be confirmed in multicenter cohort studies with relatively large populations. Furthermore, the effect of this technique on patient's health-related quality of life is still unclear. Methods: We treated patients with recalcitrant (University of Texas wound grading system 2-C to 3-D and not responding to prior routine conservative and surgical treatments for at least 8 weeks) DFUs from seven centers using TTT (a 5 â€‹cm â€‹× â€‹1.5 â€‹cm corticotomy followed by 4 weeks of medial and lateral distraction) between July 2016 and June 2019. We analyzed ulcer healing, major amputation, recurrence, health-related quality of life (physical and mental component summary scores), and complications in the 2-year follow-up. Foot arterial and perfusion changes were evaluated using computed tomography angiography and perfusion imaging 12 weeks postoperatively. Results: A total of 1175 patients were enrolled. Patients who died (85, 7.2%) or lost to follow-up (18, 1.7%) were excluded, leaving 1072 patients for evaluation. Most of the patients were male (752, 70.1%) and with a mean age of 60.4 â€‹± â€‹9.1 years. The mean ulcer size was 41.0 â€‹± â€‹8.5 â€‹cm2 and 187 (16.6%) ulcers extended above the ankle. During the follow-up, 1019 (94.9%) patients healed in a mean time of 12.4 â€‹± â€‹5.6 weeks, 53 (4.9%) had major amputations, and 33 (3.1%) experienced recurrences. Compared to preoperatively, the patients had higher physical (26.2 â€‹± â€‹8.3 versus 41.3 â€‹± â€‹10.6, p â€‹= â€‹0.008) and mental (33.6 â€‹± â€‹10.7 versus 45.4 â€‹± â€‹11.3, p â€‹= â€‹0.031) component summary scores at the 2-year follow-up. Closed tibial fracture at the corticotomy site was found in 8 (0.7%) patients and was treated using external fixation and healed uneventfully. There were 23 (2.1%) patients who had pin site infections and were treated successfully with dressing changes. Compared to preoperatively, the patients had more small arteries and higher foot blood flow (8.1 â€‹± â€‹2.2 versus 28.3 â€‹± â€‹3.9 ml/100 â€‹g/min, p â€‹= â€‹0.003) and volume (1.5 â€‹± â€‹0.3 versus 2.7 â€‹± â€‹0.4 ml/100 â€‹g, p â€‹= â€‹0.037) 12 weeks postoperatively. Conclusion: TTT promotes healing, limb salvage, and health-related quality of life in patients with recalcitrant DFUs as demonstrated in this multicenter cohort study. The surgical procedure was simple and straightforward and the complications were few and minor. The effect of this technique was associated with neovascularization and improved perfusion at the foot mediated by the cortex distraction. The findings are required to confirm in randomized controlled trials.The Translational Potential of this Article: TTT can be used as an effective treatment in patients with recalcitrant DFUs. The mechanism is associated with neovascularization and consequently increased perfusion in the foot after operation.

sncRNAs in Epididymosomes: The Contribution to Embryonic Development and Offspring Health.

Much progress has been made in determining that paternal environmental exposures can remodel their spermatozoa small noncoding RNAs (sncRANs) and, in turn, affect the phenotypes of their offspring. Studies have shown that changes in the spermatozoa sncRNAs profile occur during passing through the epididymis. Due to the absence of transcription and translation in the epididymis, spermatozoa remodel their sncRNAs profile through communication with the epididymal microenvironment. Since epididymosomes contribute to the process of spermatozoa maturation by mediating the crosstalk between the epididymis and the passing spermatozoa, they are considered to be the leading candidate to mediate these changes. Previous studies and reviews on the role of epididymal transfer proteins in sperm maturation and function are myriad. This review focuses on the role and mechanisms of epididymosome-mediated transfer of sncRNAs cargoes onembryonic development and offspring health.

Predictive Value of Adenoviral Load for Bronchial Mucus Plugs Formation in Children with Adenovirus Pneumonia.

Background: The study aimed to explore risk factors for bronchial mucus plugs (BMP) formation in children with adenovirus (AdV) pneumonia. Methods: A retrospective study was conducted on children with AdV pneumonia who underwent bronchoscopy from January 2019 to December 2019. Children were divided into the BMP group and the control group, depending on whether BMP was formed or not. The clinical information and treatment proposals of the two groups of children were counted and analyzed via multiple logistic regression analysis, ROC curve analysis, and correlation analysis. Results: Among 453 patients with AdV pneumonia, 185 (40.84%) were in the BMP group. Among all the cases, there were 188 patients with a single AdV infection, including 64 (34.04%) in the BMP group and 124 (65.96%) in the control group. The incidence of dyspnea, poor spirits, mixed infections, and other symptoms in the BMP group was higher than in the control group. Children in the BMP group had a longer heat range. C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (DD), and AdV load levels were higher in the MBP group. AdV load, Mycoplasma coinfection, DD, heat range, and LDH were independent risk factors for BMP, among which AdV load was the most significant (AUC = 0.819). AdV load was positively correlated with other risk factors, respectively. AdV load and heat range were independent risk factors for BMP patients with a single AdV infection. Conclusion: AdV load might have important clinical value in predicting BMP development in AdV pneumonia.

Analysis of the Effect of Antibiotic Bone Cement in the Treatment of Diabetic Foot Ulcer through Tibia Transverse Transport.

OBJECTIVE: To explore the efficacy of antibiotic bone cement (ABC) combined with the modified tibial transverse transport (mTTT) on the treatment of severe diabetic foot with infection. METHODS: A retrospective cohort study was conducted of 243 patients with TEXAS grade 3/4 stage D diabetic foot ulcers from December 2016 to December 2019. A total of 115 patients treated with mTTT were classified as the mTTT group (78 male and 37 female, mean age: 70.4 ± 6 years) and 128 patients who were treated with ABC combined with mTTT were in the ABC + mTTT group (89 male and 39 female, mean age: 68.9 ± 8 years). Follow-up records during treatment and 6 months after surgery were collected, including the time required for white blood cells (WBC) and C-reactive protein (CRP) to return to normal range, wound healing time, pain visual analog scale (VAS), ankle-brachial index (ABI), foot skin temperature, transcutaneous oxygen pressure measurement (TcPO2 ), complications, and other indicators. Normally distributed data were compared using the independent sample t-test, non-normally distributed data were analyzed by one-way ANOVA analysis of variance. RESULTS: There were 128 cases in the ABC + mTTT group (89 male and 39 female, mean age: 68.9 ± 8 years) treated with ABC and mTTT, and 115 cases in the TTT group (78 male and 37 female, mean age: 70.4 ± 6 years) treated with mTTT alone. The time required for WBC and CRP to return to the normal range and wound healing time in the ABC + mTTT group were significantly shorter than those in the mTTT group (12.9 ± 4.6 vs. 22.6 ± 1.6 days, t = 3.979, p < 0.001; 25.3 ± 1.3 vs. 31.3 ± 2.3 days, t = 4.261, p = 0.001; 11.9 ± 3.8 vs. 15.9 ± 3.9 days, t = 4.539, p < 0.001). There were no significant intergroup differences in the foot skin temperature, VAS score, ABI, and TcPO2 (t = 0.349, 0.542, 0.765, 0.693 while all p > 0.05). CONCLUSION: Although the application of ABC with mTTT for treatment of diabetic foot ulcers did not affect the wound healing time and ankle blood supply in the mid-term, it could control ulcer infection faster and accelerate wound healing.

Effects and Safety of Sacubitril/Valsartan for Patients with Myocardial Infarction: A Systematic Review and Meta-Analysis.

Patients who develop heart failure (HF) after an acute myocardial infarction (AMI) are at higher risk of adverse fatal and nonfatal outcomes. Studies have shown sacubitril/valsartan can further reduce the risk of cardiovascular death or hospitalization for heart failure by 20% compared with enalapril. At the same time, its tolerance and safety are better. However, the current evidence regarding the efficacy of sacubitril/valsartan in patients with heart failure after acute myocardial infarction is controversial. To assess the effect of sacubitril/valsartan on heart failure after acute myocardial infarction, we conducted a systematic review of the literature and a meta-analysis of existing randomized clinical trials. Meta-analysis of randomized controlled trails is used where data are collected from PubMed, the Cochrane library, Embase, and Web of Science. Data about sacubitril/valsartan were available from 5 studies. Forest plots showed that the sacubitril/valsartan group had a 299% higher value of sacubitril/valsartan to the control group (MD = 2.99%, 95% CI: 2.01, 3.96, I 2 = 78%, P < 0.00001, Figure 2), and the difference was statistically significant. Forest plots showed that the sacubitril/valsartan group had a 531% lower value of LVEF to the control group (MD = -5.31%, 95% CI: -7.36, -3.26, I 2 = 91%, P < 0.00001, Figure 2), and the difference was statistically significant. Forest plots showed that the sacubitril/valsartan group had a 133% lower value of NT-proBNP to the control group (MD = -1.33%, 95% CI: -1.54, -1.12, I 2 = 96%, P < 0.00001, Figure 3). Forest plots showed that the sacubitril/valsartan group had a 49% lower risk of heart failure to the control group (MD = 0.49, 95% CI: 0.27, 0.89, I 2 = 0%, P=0.02, Figure 3). The patients in experimental showed an obviously lower OR of MACE (OR = 0.47, 95% CI: 0.27, 0.82, P=0.007, Figure 3). The data were statistically significant. We have observed that for patients with heart failure after acute myocardial infarction, early administration of sacubitril/valsartan can significantly reduce the incidence of heart rate, left ventricular ejection fraction, NT-proBNP, and MACE. Our meta-analysis suggests that taking sacubitril/valsartan is relatively safe and effective, especially if started early after acute myocardial infarction.

MicroRNAs secreted by human embryos could be potential biomarkers for clinical outcomes of assisted reproductive technology.

Introduction: MicroRNAs (miRNAs) are important regulators of many biological functions, including embryo implantation and development. Recently, it has been reported that miRNAs in biofluids are predictive for physiological and pathological processes. Objectives: In this study, we aim to investigate whether the miRNAs secreted by human embryos in culture medium can be used as embryonic biomarkers. Methods: The culture media were prospectively collected from embryos of patients at reproductive medicine center with informed consent. A high-throughput miRNA sequencing method was applied to detect the miRNA profiles in the human embryo culture media. After bioinformatics analysis and screening of differentially expressed miRNAs, quantitative real-time polymerase chain reaction (qRT-PCR) assay was subsequently performed to further confirm the sequencing results with mixed samples. Furthermore, we performed droplet digital PCR (ddPCR) to verify the target miRNAs at single sample level. Receiver operating characteristic (ROC) analyses were performed for differentially expressed miRNAs. Results: Compared with embryos with failed pregnancy, the embryos with successful pregnancy secreted different miRNA profiles into the culture media, which were predicted to be involved in multiple biological processes. Validated by droplet digital polymerase chain reaction (ddPCR), the expression of hsa-miR-26b-5p and hsa-miR-21-5p in the culture media of cleavage embryos with successful pregnancy was significantly lower than that of embryos with failed pregnancy. Moreover, the Receiver Operating Characteristic (ROC) curve analysis indicated that hsa-miR-26b-5p and hsa-miR-21-5p could serve as potential biomarkers for reproductive outcomes. Conclusion: Together, our findings highlight the important predictive potential of miRNAs secreted by human embryos in culture media, which is meaningful for non-invasive embryo selection in assisted reproductive technology.

Modified tibial transverse transport technique for the treatment of ischemic diabetic foot ulcer in patients with type 2 diabetes.

BACKGROUND: Ischemic diabetic foot ulcer is one of the terminal complications of diabetes. The high amputation rate, recurrence rate, and treatment cost have caused a huge burden on patients and society. This study designed the modified tibial transverse transport (mTTT) technology to treat diabetic ischemic diabetic foot ulcers in patients with type 2 diabetes and investigated the effectiveness and safety of this technique. METHODS: This was a retrospective analysis of patients with type 2 diabetes and ischemic diabetic foot ulcers at two hospitals during January 2016-October 2019. These patients underwent mTTT surgery combined with wound debridement and vacuum sealing drainage negative pressure drainage treatment. In-hospital follow-up was performed at 1 month after the operation, while outpatient follow-up was performed at 3, 6, and 12 months after the operation. The ulcer healing time, recurrence rate, major amputation rate, and complications were analysed. RESULTS: A total of 201 patients were enrolled in this study, including 107 males and 94 females (mean age: 68.3 â€‹± â€‹7.1 years). The wounds of all patients healed completely (mean healing time: 4.6 â€‹± â€‹1.6 months). There was no occurrence of major amputation, recurrence, and treatment-related complications in the patients. CONCLUSION: mTTT can effectively and safely treat ischemic diabetic foot ulcers in patients with type 2 diabetes. This technology is an important part of the ischemic diabetic foot ulcer treatment system and warrants further research. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study introduced a new method to treat the ischemic diabetic foot ulcer which was called modified tibial transverse transport. The promising outcomes of patients indicated that this surgical method had great potential for clinical application and was worthy of further clinical research with high evidence level.

[Modified transverse tibial bone transplantation and microcirculation reconstruction for the treatment of end-stage diabetic foot].

OBJECTIVE: To explore clinical effect of modified transverse tibial bone transfer microcirculation reconstruction in treating end-stage diabetic foot. METHODS: From August 2016 to June 2018, 87 patients with diabetic foot treated with modified tibial transverse bone removal and microcirculation reconstruction, inclduing 54 males and 33 females;aged from 39 to 95 years old with an average of (68.9±11.3) years old;2 patients were grade 2, 37 patients were grade 3 and 50 patients were grade 4 according to Wagner's classification;the courses of diabetic were for 10 to 16 years with an average of (13.0±2.2) years;the courses of diabetic feet were for 21 to 48 days with an avergae of (34.2±8.6) days. Postoperative comlications were observed. Skin temperature, visual analogue scale(VAS) and ankle brachial index(ABI) and wound healing were recorded before and 3 months after operation. RESULTS: All patients were followed up for 4 to 19 months with an average of (12.6±2.8) months. Two patients occurred subcutaneous tissue liquefaction and seepage under needle passage during bone transfer, and scabed without special treatment. One patient was performed amputation above 5 cm of ankle joint because of severe infection, and 1 patient occurred re-ulceration at 1 year after wound healing, bone transfer was performed again at the same site, and was completely healed at 8 weeks after operation. The healing time of wound ranged from 3 to 24 weeks with an average of (11.9± 3.8) weeks. Foot skin temperature before operation was (28.9±0.91) ℃, and increased to (31.70±0.32)℃ at 3 months after operation(t=5.72 P=0.006);VAS score before opertaion was (7.80±0.72), and improved to (2.20±0.13) at 3 months after operation (t=25.38, P=0.000);ABI beforeoperation was(0.48±0.30), increased to(0.98±0.24) at 3 months after oeprtaion(t= 14.68, P=0.000). CONCLUSION: Modified lateral tibial bone transfer could effectively reconstruct microvascular network under lower leg, promote recovery of peripheral blood vessels, and promote wound healing of foot, reduce or avoid amputation. At the same time, the improved osteotomy is one of the effective methods for the treatment of diabetic foot which has advantags of less trauma, simple opertaion.

Disseminated Talaromyces marneffei Infection in a Non-HIV Infant With a Homozygous Private Variant of RELB.

Objective: This study presents a relatively rare case of disseminated Talaromyces marneffei (T. marneffei) infection in an HIV-negative patient. Methods: An 8-month-old girl was hospitalized because of uncontrollable fever and cough for 6 days. Routine laboratory tests, biochemical detection, immunological tests, pathogenic examination, and imaging inspection were performed. Genetic tests of trio whole genome sequencing (Trio-WES), trio copy number sequencing (Trio-CNVseq), and Sanger sequencing were conducted to identify pathogenic variants. In silico analysis of the sequence alignment and structural modeling results was carried out to study the possible pathogenicity of the identified variant. Western blotting was performed to investigate the expression of the identified gene at the protein level. Results: Enhanced CT and MRI scanning demonstrated thymic dysplasia, diffuse pulmonary and liver nodules, and many balloon-like air sacs in both lungs. The white blood cell count, neutrophil count, and neutrophil ratio were normal or elevated. The patient was HIV-negative and bone marrow and blood culture showed T. marneffei infection. Total lymphocyte count, CD3+ T lymphocyte count, CD3+CD4+ T lymphocyte count, CD3+CD8+ T lymphocyte count, and NK cell count decreased, while the number of CD19 positive B cells increased. However, the ratio of CD3+CD4+:CD3+CD8+ T cells increased. Trio-WES identified a homozygous private variant of NM_006509: c.400_c.401insAGC/p.Lys134 delinsLysGln in RELB and Sanger sequencing validated the result. Structural modeling indicated that the variant may be pathogenic. Reverse transcription-polymerase chain reaction and Western blot analysis showed that the expression of RelB in the patient was lower than that in the healthy controls at mRNA and protein levels. Conclusion: This is the first report on disseminated T. marneffei infection in a patient with a homozygous private variant of RELB.

Radiation-induced eosinophils improve cytotoxic T lymphocyte recruitment and response to immunotherapy.

The efficacy of cancer immunotherapy is dictated by CD8+ T cell infiltration and the nature of the tumor microenvironment (TME). By inflaming the TME to favor CD8+ T cell immunity, radiation is now widely considered as a neoadjuvant for immunomodulation. Here, we observed that local irradiation enhances the infiltration of intratumoral eosinophils, and depletion of eosinophil dampens CD8+ T cell infiltration and diminishes the anti-tumor effectiveness of radiation. Retrospectively, we identified a strong correlation between eosinophilia and survival benefit in radiation-treated cancer patients. Experimentally, we further show that radiation enhances the intratumoral infiltration of adoptive transferred T cells therapy, bolstering eosinophils by intravenous interleukin-5 administration promotes the efficacy of radiation-induced abscopal effect. Together, these results suggest that eosinophil mobilization can be considered as a mechanistically relevant biomarker for predicting the effectiveness of pre-immunotherapy radiation, as well as a new strategy to enhance T cell-mediated immunotherapy against cancers.

Effects of functional electrical stimulation on neuromuscular function after targeted muscle reinnervation surgery in rats.

the purpose of targeted muscle reinnervation (TMR) surgery is to provide more electromyography information for prosthetic control by reconstructing the deconstructed structure between the distal nerve and the stump muscle. Functional electrical stimulation (FES) of denervated muscles or proximal nerve stump after peripheral nerve surgery can effectively promote nerve regeneration and muscle function recovery. This pilot divided SD adult male rats into normal control group, denervation group, TMR group, and FES group according to whether they received TMR surgery and whether they received FES after surgery. The results showed that low-frequency electrical stimulation treatment could effectively promote transplanted nerve regeneration and significantly enhances motor function of target muscles.Clinical Relevance-This experiment successfully established TMR rat models, and explored the recovery of injured neuromuscular function by using electrodes implanted intramuscularly and analyzing myoelectric signals, and the use of low-frequency electrical stimulation treatment had a positive effect on the regeneration of the transplanted nerve.

[Clinical effect of propranolol in the treatment of respiratory hemangioma in infants and young children].

OBJECTIVE: To study the clinical effect of oral propranolol in the treatment of respiratory hemangioma in infants and young children. METHODS: A retrospective analysis was performed from the chart review data of children with respiratory hemangioma treated by oral propranolol and diagnosed by bronchoscopy and laryngeal plain enhanced CT/MRI from November 2012 to December 2019. RESULTS: A total of 20 children were enrolled. All children had improvement in the symptoms of laryngeal stridor and dyspnea after oral administration of propranolol for 1-2 days. The median treatment time was 10 months (range 6-12 months). The median follow-up time was 10 months (range 3-15 months). Of the 20 children, 19 (95%) achieved regression of tumor, and 1 (5%) experienced an increase in tumor size during reexamination at 6 months after drug withdrawal and had no recurrence after the treatment with an increased dose of propranolol for 6 months. Only 1 child (5%) had adverse reactions, and 1 child (5%) was still under treatment. CONCLUSIONS: Oral propranolol can quickly relieve the symptoms such as dyspnea and achieve tumor regression, with few adverse events, and it is therefore an effective method for the treatment of respiratory hemangioma in infants and young children.

Frequent and mild scrotal heat stress in mice epigenetically alters glucose metabolism in the male offspring.

Several studies have reported that health problems occur in assisted reproductive technology (ART)-conceived offspring. Recently, investigations have demonstrated that paternal environmental conditions influence offspring health. However, it is unclear whether the factors that cause male infertility per se affect offspring health and contribute to health problems in ART-born children. Scrotal heat stress represents a common cause for oligoasthenozoospermia, and in these cases, in vitro fertilization-embryo transfer (IVF-ET) is typically recommended for those individuals trying to conceive. We exposed C57BL/6J male mice to frequent and mild scrotal heat stress (fmSHS) (39°C for 30 min once weekly for 5 consecutive wk). Sperm was subjected to IVF-ET with oocytes of untreated C57BL/6J females to produce offspring mice. Glucose intolerance and insulin resistance was observed in the male offspring mice derived from fmSHS-exposed fathers. Islets, after evaluation, remained unchanged. Genes involved in glucose metabolism, especially, those in insulin signaling pathways, showed dysregulation in the liver of the fmSHS-derived male offspring. Differentially methylated regions were found in the sperm of fmSHS-exposed mice by whole genome bisulfite sequencing. Interestingly, abnormal methylation of some genes with altered expression in offspring was observed in both the sperm of fmSHS fathers and the liver of their male offspring. Our results suggest that the factors that cause male infertility can affect male offspring health by an epigenetic mechanism.

Heat Stress and Pulsed Unfocused Ultrasound: The Viability of these Physical Approaches for Drug Delivery into Testicular Seminiferous Tubules.

AIM: To investigate the application of Scrotal Heat Stress (SHS) and Pulsed Unfocused Ultrasound (PuFUS) to explore Blood-Testis Barrier (BTB) permeability in adult mice. BACKGROUND: The BTB provides a stable microenvironment and a unique immune barrier for spermatogenesis. Meanwhile, it blocks macromolecular substances access, including therapeutic agents and antibodies, thereby it decreases the therapeutic or immunocontraception effects. OBJECTIVES: To determine the viability of these physical approaches in delivering macromolecular substances into seminiferous tubules. MATERIALS & METHODS: Mice were subjected to receive single SHS intervention at 39°C, 41°C, or 43°C for 30 min. Whereas, mice received the PuFUS intervention at 1.75w/cm2, 1.25w/cm2, and 2.5w/cm2 for 2 min, 5 min, and 10 min, respectively. The Biotin and macromolecular substances (IgG, IgM, and exosomes) were separately injected into the testicular interstitium at different times following SHS or PuFUS interventions, to observe their penetration through BTB into seminiferous tubules. RESULTS: As detected by Biotin tracer, the BTB opening started from day-2 following the SHS and lasted for more than three days, whereas the BTB opening started from 1.5h following PuFUS and lasted up to 24h. Apparent penetration of IgG, IgM, and exosomes into seminiferous tubules was observed after five days of the SHS at 43°C, but none at 39°C, or any conditions tested with PuFUS. CONCLUSION: The current results indicate that SHS at 43°C comparatively has the potential for delivering macromolecular substances into seminiferous tubules, whereas the PuFUS could be a novel, quick, and mild approach to open the BTB. These strategies might be useful for targeted drug delivery into testicular seminiferous tubules. However, further studies are warranted to validate our findings.