Modified black phosphorus quantum dots promotes spinal cord injury repair by targeting the AKT signaling pathway.

Spinal cord injury (SCI) is a serious refractory disease of the central nervous system (CNS), which mostly caused by high-energy trauma. Existing interventions such as hormone shock and surgery are insufficient options, which relate to the secondary inflammation and neuronal dysfunction. Hydrogel with neuron-protective behaviors attracts tremendous attention, and black phosphorus quantum dots (BPQDs) encapsulating with Epigallocatechin-3-gallate (EGCG) hydrogels (E@BP) is designed for inflammatory modulation and SCI treatment in this study. E@BP displays good stability, biocompatibility and safety profiles. E@BP incubation alleviates lipopolysaccharide (LPS)-induced inflammation of primary neurons and enhances neuronal regeneration in vitro. Furthermore, E@BP reconstructs structural versus functional integrity of spinal cord tracts, which promotes recovery of motor neuron function in SCI rats after transplantation. Importantly, E@BP restarts the cell cycle and induces nerve regeneration. Moreover, E@BP diminishes local inflammation of SCI tissues, characterized by reducing accumulation of astrocyte, microglia, macrophages, and oligodendrocytes. Indeed, a common underlying mechanism of E@BP regulating neural regenerative and inflammatory responses is to promote the phosphorylation of key proteins related to AKT signaling pathway. Together, E@BP probably repairs SCI by reducing inflammation and promoting neuronal regeneration via the AKT signaling pathway.

Exosome-based strategy for degenerative disease in orthopedics: Recent progress and perspectives.

Background: Degenerative diseases in orthopaedics have become a significant global public health issue with the aging of the population worldwide. The traditional medical interventions, including physical therapy, pharmacological therapy and even surgery, hardly work to modify degenerative progression. Stem cell-based therapy is widely accepted to treat degenerative orthopaedic disease effectively but possesses several limitations, such as the need for strict monitoring of production and storage and the potential risks of tumorigenicity and immune rejection in clinical translation. Furthermore, the ethical issues surrounding the acquisition of embryonic stem cells are also broadly concerned. Exosome-based therapy has rapidly grown in popularity in recent years and is regarded as an ideal alternative to stem cell-based therapy, offering a promise to achieve 'cell-free' tissue regeneration. Methods: Traditionally, the native exosomes extracted from stem cells are directly injected into the injured site to promote tissue regeneration. Recently, several modified exosome-based strategies were developed to overcome the limitations of native exosomes, which include mainly exogenous molecule loading and exosome delivery through scaffolds. In this paper, a systematic review of the exosome-based strategy for degenerative disease in orthopaedics is presented. Results: Treatment strategies based on the native exosomes are effective but with several disadvantages such as rapid diffusion and insufficient and fluctuating functional contents. The modified exosome-based strategies can better match the requirements of the regeneration in some complex healing processes. Conclusion: Exosome-based strategies hold promise to manage degenerative disease in orthopaedics prior to patients reaching the advanced stage of disease in the future. The timely summary and highlights offered herein could provide a research perspective to promote the development of exosome-based therapy, facilitating the clinical translation of exosomes in orthopaedics. Translational potential of this article: Exosome-based therapy is superior in anti-senescence and anti-inflammatory effects and possesses lower risks of tumorigenicity and immune rejection relative to stem cell-based therapy. Exosome-based therapy is regarded as an ideal alternative to stem cell-based therapy, offering a promise to achieve 'cell-free' tissue regeneration.

Treatment Effect of Mometasone Furoate Cream on Lichen Sclerosus et Atrophicus of External Genitalia in Boys and Its Correlation with Toll-Like Receptor 4 and Myeloid Differentiation Factor 88.

Objective: The objective is to explore the treatment effect of mometasone furoate cream on lichen sclerosus et atrophicus (LSeA) of external genitalia in boys and its correlation with Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Methods: A total of 100 boys treated in our hospital from January 2021 to January 2023 due to clinical manifestations in the external genitalia were selected as the study objects. All boys received redundant circumcision treatment, their protein expression of TLR4 and MyD88 in foreskin tissues was measured by BCA protein assay and western blot, and mometasone furoate cream was applied to those who were pathologically diagnosed with LSeA, so as to compare the levels of serum inflammatory factors and urodynamic indicators in the child patients before and after treatment. Results: The total clinical efficacy rate of LSeA child patients was up to 90.79%; after treatment, the maximum and mean urinary flow rates of child patients were significantly higher than before treatment (P < 0.001); compared with the non-LSeA group, the protein expression of TLR4, MyD88, and NF-κB was increased in the LSeA group (P < 0.001), and the mRNA expression of TLR4, MyD88, and NF-κB was significantly increased in the LSeA group (P < 0.001); the results of ROC curves showed that TLR4 had the highest AUC value, and during treatment, the incidence rate of adverse reactions in child patients was 6.58%. Conclusion: LSeA will increase the inflammatory reactions in child patients, and its pathogenesis may be related to the upregulation of TLR4, MyD88, NF-κB expression and thus activation of TLR4/MyD88/NF-κB signaling pathways. Applying mometasone furoate cream to LSeA patients after redundant circumcision can effectively reduce the inflammatory reactions in the body and improve their urodynamic indicators, with exact efficacy. Further research will be conducive to establishing a better treatment scheme for such child patients.

Usage of intermingled skin allografts and autografts in a senior patient with major burn injury.

Mortality rate in older adults following extensive burn injury is extremely high, and management of these patients is challenging. One of the main problems is that autologous split-thickness skin grafts are scarce and the wounds cannot be covered quickly and effectively. Intermingled skin grafting is a low-tech and economic method, which not only maximizes the use of precious autologous skin but also prevents the wounds from infection and consumption. Herein we present a case of extensive burn injury in a 68-year-old female successfully treated with intermingled skin grafting. The patient was accidentally burned by gas flame, resulting in a major burn injury covering 80% of her total body surface area. Early burn wound excision was performed and the wound was temporarily covered with irradiated porcine skin in the first week after injury. Autologous stamp-like skin grafts were applied to the wound bed 4 weeks after injury. In this operation, the results were not satisfactory. The take rate of the skin grafts is only about 50%. We covered the wounds with intermingled skin allografts and autografts 8 weeks after injury: autografts (0.5 cm × 0.5 cm) + fresh close relative's allografts (1 cm × 1 cm) + cryopreserved allografts (2 cm × 2 cm).

[Analysis on the diagnosis and treatment of necrotizing fasciitis complicated with sepsis].

OBJECTIVE: To recognize the characteristics of necrotizing fasciitis patients complicated with sepsis and summarize the experience the treatment. METHODS: A retrospective study was conducted. The clinical data of 57 patients with necrotizing fasciitis complicated with sepsis admitted to Guangdong Provincial People's Hospital from July 2009 to December 2019 was analyzed by collecting such factors as gender, age, complications, infection sites, pathogens, surgery information, treatment options and outcome. The patients were divided into debridement group (n = 14) and control group (n = 43) according to whether the debridement was completed within 48 hours of admission, and the mortality during hospitalization between the two groups was compared. A telephone follow-up had been done to record the long-term outcome of these patients. RESULTS: Among 57 patients with necrotizing fasciitis complicated with sepsis, there were 43 males and 14 females with the average age of (57.9±12.1) years old. Most of the underlying diseases were diabetes mellitus (70.17%), other diseases included hypertension (8.77%), tumor chemotherapy (7.02%), liver disease (hepatitis, cirrhosis, 7.02%), coronary artery heart disease (3.51%), systemic lupus erythematosus (3.51%), etc. Most of the infection site was lower limbs (71.93%). There were 78 pathogens cultured in 57 patients, in which 52 were non-drug resistant bacteria (66.67%), and 26 were drug resistant bacteria (33.33%). There were 40 Gram positive (G+) bacteria (51.28%), 29 Gram negative (G-) bacteria (37.18%), 8 fungi (10.26%) and 1 mixed bacteria (1.28%). Finally, of 57 patients, 46 patients were cured, and 11 patients died with hospital mortality of 19.30%. Among 57 patients, the hospital mortality in the debridement group was significantly lower than that in the control group [0% (0/14) vs. 25.58% (11/43), P < 0.05]. Among the 46 cured patients, 11 had accepted amputations, accounting for 23.91%. In December 2020, 43 patients who were cured (3 patients were lost to follow-up) were followed up by telephone. Twenty-three patients were completely self-care, 9 patients were partly self-care, 8 patients were completely unable to take care of themselves, and 3 patients died. CONCLUSIONS: Necrotizing fasciitis with sepsis mostly occurs in people with weakened immunity, and has a high mortality and disability rate. Early identification and active surgical debridement may be the key to improve the treatment effect.

TERT rs10069690 polymorphism and cancers risk: A meta-analysis.

BACKGROUND: Studies have identified that the telomerase reverse transcriptase (TERT) gene polymorphism rs10069690 (C>T) is associated with cancer risk, but the results remain inconclusive. METHODS: To provide a more precise estimation of the relationship, we performed a meta-analysis of 45 published studies including 329,035 cases and 730,940 controls. We conducted a search in PubMed, Google Scholar and Web of Science to select studies on the association between rs10069690 and cancer risk. Stratification by ethnicity, cancer type, cancers' classification, source of control, sample size, and genotype method was used to explore the source of heterogeneity. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were evaluated using random effects models. Sensitivity, publication bias, false-positive report probability (FPRP) and statistical power were also assessed. RESULTS: The result demonstrated that rs10069690 was significantly associated with an increased risk of cancer overall (OR = 1.09, 95% CI: 1.06-1.12, p < .001) under the allele model. Stratification analysis revealed an increased cancer risk in subgroups of breast cancer, ovarian cancer, lung cancer, thyroid cancer, and renal cell carcinoma (RCC). However, a significantly decreased association was observed in pancreatic cancer in the European population (OR = 0.93,95% CI: 0.87-0.99, p = .031). In the subgroup analysis based on cancer type, no significant association was found in prostate cancer, leukemia, colorectal cancer and glioma. CONCLUSIONS: This meta-analysis suggested that the TERT rs10069690 polymorphism may be a risk factor for cancer, especially breast cancer, ovarian cancer, lung cancer, thyroid cancer, and RCC. Further functional studies are warranted to reveal the role of the polymorphism in carcinogenesis.

Evaluation of GALNT16 polymorphisms to breast cancer risk in Chinese population.

BACKGROUND: Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16) is an N-acetylgalactosaminyltransferase gene that alters protein O-glycosylation, which plays a role in tumor development. This study aims to explore the association of eight GALNT16 polymorphisms with susceptibility to breast cancer (BC). METHODS: This case-control study included 563 BC patients and 552 age-matched healthy controls from the Chinese Han population. The genotypes of GALNT16 polymorphisms were detected using the Agena MassARRAY. The relationship between GALNT16 polymorphisms and BC risk was evaluated using a chi-squared test with an odds ratio (OR) and 95% confidence intervals (CI) under five genetic models. RESULTS: We observed that rs2105269 and rs72625676 were associated with higher BC risk in younger patients with age ≤51 (rs2105269, codominant: p = .006; recessive: p = .005 additive: p = .018; and allele: p = .012; rs72625676, codominant: p = .038; recessive: p = .037). For rs1275678 polymorphism, there was a significantly decreased risk of BC among elder patients (codominant: p = .017; dominant: p = .019; additive: p = .030; and allele: p = .029). Further analysis by clinical characteristics showed rs2105269 was associated with tumor size and lymph node metastasis. CONCLUSION: Our study suggests that GALNT16 polymorphisms are associated with BC susceptibility in Chinese population.

Analysis of MIR155HG variants and colorectal cancer susceptibility in Han Chinese population.

BACKGROUND: MIR155HG plays an important role in malignant tumors, but it is rarely reported in the occurrence and development of colorectal cancer (CRC). This study investigated the effects of MIR155HG polymorphisms on CRC susceptibility from the perspective of molecular genetics. METHODS: Eight SNPs in MIR155HG were selected and genotyped among 514 CRC cases and 510 healthy controls using the Agena MassARRAY platform. The associations between these SNPs and the CRC risk were evaluated under genetic models using conditional logistic regression analysis. The HaploReg v4.1 database was used for SNPs functional prediction. RESULTS: The allele "C" of rs12482371 (p = 0.047), allele "C" of rs1893650 (p = 0.025), and the allele "A" of rs928883 (p = 0.037) in MIR155HG were significantly associated with CRC risk. Genetic model analysis revealed that rs12482371 and rs1893650 increased CRC risk; whereas rs928883 was associated with reduced CRC risk. Stratification analysis showed that rs9383938 was a protective factor in CRC patients under 60 years old. Rs12482371 and rs1893650 were associated with the CRC risk in females. Rs11911469 and rs34904192 may affect the clinical stage and lymph node metastasis. Moreover, the haplotypes CTT and GTC of LD block rs4143370|rs77218221|rs12482371, and the haplotypes CATGA and CACGG of LD block rs77699734|rs11911469|rs1893650|rs34904192|rs928883 were significantly associated with CRC risk. CONCLUSION: This study revealed that MIR155HG SNPs were associated with CRC susceptibility and could be predictive biomarkers for CRC risk.

[Protective effects of valproic acid on gut barrier function after major burn injury and its mechanism].

OBJECTIVE: To investigate the potential protective effects of valproic acid (VPA) on gut barrier function after major burn injury in rats and its mechanism. METHODS: Forty male Sprague-Dawley (SD) rats were divided into sham + normal saline (NS), sham + VPA, scald + NS, and scald + VPA groups, with 10 rats in each group. Rat with 55% total body surface area (TBSA) third-degree severe-burns model was reproduced by immersing into 80 °C water, and the rats in sham groups were given sham-burns by immersing into 37 °C water. The rats after severe-burns were immediately treated with 0.25 mL of 300 mg/kg VPA or NS by subcutaneous injection. Rats were sacrificed at 2 hours and 6 hours after injury, and abdominal aortic blood and ileal tissue were harvested. The levels of vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA). The intestinal permeability was evaluated by fluorescein isothiocyanate-dextran (FITC-dextran) determination. The histomorphological changes in gut barrier were evaluated by Chiu grading system. Levels of acetylated lysine at the ninth position of histone 3 protein (Ac-H3K9), hypoxia-inducible factor 1α (HIF-1α), zona occludens 1 (ZO-1) and myosin light chain kinase (MLCK) were determined by immunofluorescence staining and Western Blot. RESULTS: Compared with sham + NS group, rats in scald + NS group showed intestinal mucosal damage 2 hours after burn injury, as well as increased mucosal permeability, protein expression levels of HIF-1α, VEGF, MLCK, and lowered levels of AC-H3K9 and ZO-1. These changes were much more prominent at 6 hours after injury. VPA treatment significantly attenuated the burn-induced intestinal damage. Compared with scald + NS group, the protective effects in scald + VPA group was not evident at 2 hours after injury; however, intestinal damage was much less severe at 6 hours after injury (Chiu score: 2.03±0.27 vs. 3.12±0.15), intestinal permeability was significantly decreased [FITC-dextran (µg/L): 709±76 vs. 1 138±75], histone acetylation was enhanced [Ac-H3K9 (gray value): 1.55±0.12 vs. 0.48±0.12], ZO-1 degradation was significantly inhibited (gray value: 0.69±0.12 vs. 0.43±0.16), the protein expression levels of VEGF and MLCK were significantly down-regulated [VEGF (ng/mg): 51.7±3.7 vs. 71.2±4.3, MLCK (gray value): 1.98±0.20 vs. 2.80±0.24], while the HIF-1α protein expression levels were significantly reduced at both 2 hours and 6 hours after injury (gray value: 2.50±0.39 vs. 3.88±0.42 at 2 hours, 1.83±0.42 vs. 4.42±0.41 at 6 hours, all P < 0.05). CONCLUSIONS: Severe burn injury can induce histone deacetylation, ZO-1 degradation and intestinal barrier dysfunction. VPA can improve the levels of histone acetylation and ZO-1, and protect intestinal epithelial barrier function. These may probably be mediated through inhibiting HIF-1α and its downstream gene VEGF and MLCK.

[Analysis of liver damage and reactivation of hepatitis B virus in hepatitis B surface antigen positive patients after extremely severe burn injury].

OBJECTIVE: To analyze the development of liver damage and reactivation of hepatitis B virus (HBV) during the treatment of extremely severe burn injury in HBsAg positive patients, in order to provide reference for prevention and treatment of liver damage in patients with HBV infection after extremely severe burn. METHODS: Medical records of 54 HBsAg positive patients after extremely severe burn injury admitted from January 2004 to December 2014 were retrospectively analyzed. Development of liver damage and HBV reactivation of these patients during the treatment were analyzed according to the classification of their gender, results of hepatitis B e antigen (HBeAg) and HBV DNA examinations on admission, and development of sepsis in the process of treatment. Data were processed with chi-square test. RESULTS: (1) The incidence of liver damage in the process of treatment of these patients was 85.2% (46/54). Among all the patients, the proportion of liver damage was 35/38 in male, which was significantly higher than that in female (11/16, χ² = 4.867, P<0.05). Liver damage was found in all of 26 patients who were HBeAg positive on admission, 34 patients who were HBV DNA positive on admission, and 36 patients who developed sepsis in the process of treatment; the proportions were significantly higher than those in patients who were HBeAg negative on admission (20/28), patients who were HBV DNA negative on admission (12/20), and patients who did not develop sepsis in the process of treatment (10/18), with χ² values respectively 11.801, 18.384, and 20.574, P values below 0.01. (2) The incidence of HBV reactivation in these patients was 29.6% (16/54). Among all the patients, the proportion of HBV reactivation was 13/38 in male and 3/16 in female, with no statistically significant difference between them (χ² = 0.656, P>0.05). The proportions of HBV reactivation in patients who were HBeAg positive on admission, patients who were HBV DNA positive on admission, and patients who developed sepsis in the process of treatment were respectively 13/26, 16/34, and 15/36, and they were significantly higher than those in patients who were HBeAg negative on admission (3/28), patients who were HBV DNA negative on admission (0/20), and patients who did not develop sepsis in the process of treatment (1/18), with χ² values respectively 9.979, 18.615, and 5.873, P<0.05 or P<0.01. CONCLUSIONS: Patients who are HBsAg positive, HBeAg positive, HBV DNA positive on admission, and develop sepsis in the process of treatment of extremely severe burn injury are more likely to develop liver damage and HBV reactivation. It is necessary to dynamically monitor the changes in HBV DNA and liver function, in order to identity the reactivation of virus.

[Classification and management of sternal wound complications after cardiac surgery].

OBJECTIVE: To define the classification of sternal wound complications after cardiac surgery and to explore the appropriate surgical treatment. METHODS: Between July 2008 and January 2014, 260 patients with sternal wound complications after cardiac surgery were treated. There were 124 males and 136 females, aged 11-75 years (mean, 49.5 years). The disease duration was 13-365 days (mean, 26.6 days) with a wound length of 1-25 cm (mean, 13.4 cm). The wounds were divided into type I (n = 70), type II (n = 64), type III (n = 42), type IV (n = 78), and type V (n = 6) according to self-generated classification for sternal wound complications after cardiac surgery. After debridement, wounds of type I and type II were repaired with local flap transplantation; wounds of type III were repaired with local flap transplantation combined with butterfly sternal fixation (n = 28), with bilateral pectoralis muscle flap combined with butterfly sternal fixation (n = 11), and with bilateral pectoralis muscle flap (n = 3); wounds of type IV were repaired with bilateral pectoralis muscle flap (n = 65), rectus abdominis muscle flap (n = 5), and pedicled omental flap (n = 8); and wounds of type V were repaired with pedicled omental flap. RESULTS: All the operations were successfully performed. Three patients died after pedicled omental flap repair, including 1 case of type IV and 2 cases of type V. The hospitalization time were 4-86 days (mean, 18.3 days). Primary wound healing was obtained in 248 cases (96.5%); poor healing occurred in 9 patients, which were cured after second surgery in 8 cases and after the third surgery in 1 case. CONCLUSION: The surgical treatment based on self-generated classification is appropriate to sternal wound complications after cardiac surgery. It can provide clinical evidence for the choice of subsequent operation.

[Effect of bone marrow mesenchymal stem cells on lipopolysacharide-induced secretion of inflammatory cytokines in rat macrophages in vitro].

OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) on secretion of inflammatory cytokines in macrophages stimulated by lipopolysacharide (LPS). METHODS: Rat BMSCs and macrophages were isolated, cultured, and identified. The BMSCs and macrophages, cultured alone or in co-culture, were treated with LPS or PBS or without treatment and tested for interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) concentrations in the supernatants at 1, 3, 5, 7, 12, and 24 h after the treatment using enzyme-linked immunosorbent assay. RESULTS: Exposure to LPS caused significantly increased IL-10 and TNF-α concentrations in the supernatant of cultured macrophages but not in BMSC culture. Macrophages co-cultured with BMSCs showed significantly lowered IL-10 and TNF-α secretions in response to LPS exposure as compared with the macrophages cultured alone. CONCLUSION: BMSCs can reduce LPS-induced secretion of inflammatory cytokines by the macrophages to ameliorate inflammatory reactions.

[Establishment of a rat model of bone marrow mesenchymal stem cell transplantation for repairing full-thickness skin defect].

OBJECTIVE: To establish a rat model of full-thickness skin defect to receive bone marrow mesenchymal stem cell transplantation for wound repair. METHODS: A full-thickness skin defect measuring 4 cmx4 cm in 36 F344 rats, which were divided into 3 groups with the wound covered with alloskin graft, acellular dermal matrix, or petrolatum gauze. In vitro cultured BMSCs in the 5th passage were transplanted into the skin defect, and the time of wound dressing dissociation and number of transplanted Brdu-positive cells in the wound were observed 14 days later. RESULTS: The alloskin graft resulted in significantly longer time before dressing dissociation, with greater number of Brdu-positive cells in the wound than the other two wound dressings (P<0.001). The acellular dermal matrix showed better effect than petrolatum gauze in terms of the dressing dissociation time and the viable transplanted cell number in the wound. CONCLUSION: Alloskin graft can be ideal for covering the wound surface to protect the transplanted BMSCs in rats.

Creation of the technique of interspecific hybridization for breeding in cotton.

The new technique of interspecific hybridization was created in Gossypium which could remarkably overcome abortion of interspecific hybridization and hybrid sterility of F(1). A large number of germplasm resources were obtained from seventy cross combinations among the cultivated species and between the cultivated and the 14 wild species, respectively. 8 varieties have been developed, of which 4 were from the cross combination of G. hirsutum x G. arboretum and the other are the first breed from the hybrids between G. hirsutum and 4 wild species, respectively. Of them Shiyuan 321 (jimian 24) is a new variety which had the highest increase in the national Yellow River Valley Regional test, with planting area added up to 933333 ha in the recent three years. The breeding system of interspecific hybridization was established.