Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Currently, there are limited strategies for convenient and rapid wound repair in clinical practice. In recent years, in-situ cell electrospinning (IS-CE) technology, developed from in-situ electrospinning (IS-E) technology, has emerged. IS-CE technology involves encapsulating living cells within micro-nanofibers to construct living fibrous tissue scaffolds in situ, making some progress in wound repair applications. However, this technology still faces limitations such as low cell survival rate and poor fiber stability. This article provides a comprehensive review on the current status of both IS-E and IS-CE technologies, as well as the application of IS-CE technology in wound repair. In addition, the advantages, limitations, and improvement methods of IS-CE technology applied in wound treatment are emphatically discussed, aiming to provide insights for its application in tissue engineering and wound repair.

Objective To investigate the risk factors and diagnostic value of severe acute kidney injury(AKI)after type A aortic dissection,and to analyze the efficacy of different dialysis strategies of renal replace-ment therapy on severe AKI.Methods The clinical data of 69 patients with severe AKI after type A aortic dissection operation in this hospital from January 2019 to December 2021 were retrospectively collected.The patients were divided into the severe group(dialysis treatment,24 cases)and the mild group(without conduc-ting filtration treatment,45 cases).The clinical data were compared between the two groups,and the risk fac-tors and diagnostic value for the severe AKI occurrence after type A aortic dissection surgery by univariate and multivariate regression and receiver operating characteristic(ROC)curve.The changes of postoperative treat-ment indicators were compared and the efficacy of different dialysis strategies were analyzed.Results The in-cidence rate of severe AKI after surgery was 34.78％.The univariate and multivariate logistic regression ana-lyses results showed that preoperative serum creatinine increase(OR=0.98,95％CI:0.97-0.99,P=0.02),total extracorporeal circulation time prolongation(OR=0.99,95％CI:0.97-0.99,P=0.02)and postopera-tive 24 h blood transfusion volume increase(OR=0.99,95％CI:0.98-0.99,P＜0.01)were the independent risk factors for postoperative severe AKI occurrence in the patients with type A aortic dissection.The ROC curve analysis suggested that the combination of total time of extracorporeal circulation,preoperative serum creatinine value and postoperative 24 h blood transfusion volume had good diagnostic value for postoperative severe AKI occurrence in the patients with type A aortic dissection.The sensitivity,specificity and area under the curve were 91.10％,75.00％and 0.90 respectively.Early performing filtration and continuous renal re-placement therapy(CRRT)in the severe AKT had better effect.Conclusion The independent risk factors for postoperative severe AKI occurrence in type A aortic dissection include preoperative serum creatinine in-crease,intraoperative total extracorporeal circulation time prolongation and postoperative 24 h blood transfu-sion volume increase,and the three combination has good predictive value for severe AKI.Early detection and timely using renal replacement therapy could improve severe AKI,CRRT has a better effect for AKI than in-termitlent hemodialysis(IHD).

Objective:To observe the effect of combining robot-assisted gait training (RAGT) with task-oriented training (TOT) on the walking ability of children with dyskinetic cerebral palsy (DCP).Methods:Sixty DCP children were randomly divided into a conventional intervention group, an RAGT group, and a combined intervention group, each of 20. All of the children received conventional rehabilitation therapy, while the RAGT and combined intervention groups were additionally provided with RAGT, and RAGT combined with TOT, respectively. Before the experiment and after 12 and 24 weeks of treatment, the subjects′ walking ability was evaluated using the 10-metre walk test (10MWT), and the D energy zone (standing position) and the E energy zone (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument.Results:After 12 and 24 weeks of treatment, the average 10MWT speed and D and E energy zone scores of all three groups had improved significantly. After 24 weeks the combined group′s averages on all three measures were significantly better than those of the other two groups.Conclusion:RAGT combined with TOT and conventional rehabilitation training significantly improves the walking ability of DCP children.

BACKGROUND: Exosomes derived from breast cancer have been reported to play a role in promoting cell proliferation, migration, and angiogenesis, which has the potential to accelerate the healing process of diabetic wounds. The aim of this investigation was to examine the function of exosomes originating from 4T1 mouse breast carcinoma cells (TEXs) in the process of diabetic wound healing. METHODS: The assessment of primary mouse skin fibroblasts cell proliferation and migration was conducted through the utilization of CCK-8 and wound healing assays, while the tube formation of HUVECs was evaluated by tube formation assay. High-throughput sequencing, RT-qPCR and cell experiments were used to detect the roles of miR-126a-3p in HUVECs functions in vitro. The in vivo study employed a model of full-thickness excisional wounds in diabetic subjects to explore the potential therapeutic benefits of TEXs. Immunohistochemical and immunofluorescent techniques were utilized to evaluate histological changes in skin tissues. RESULTS: The findings suggested that TEXs facilitate diabetic wound healing through the activation of cell migration, proliferation, and angiogenesis. An upregulation of miR-126a-3p has been observed in TEXs, and it has demonstrated efficient transferability from 4T1 cells to HUVEC cells. The activation of the PI3K/Akt pathway has been attributed to miR-126a-3p derived from TEXs. CONCLUSIONS The promotion of chronic wound healing can be facilitated by TEXs through the activation of cellular migration, proliferation, and angiogenesis. The activation of the PI3K/Akt pathway by miR-126a-3p originating from TEXs has been discovered, indicating a potential avenue for enhancing the regenerative capabilities of wounds treated with TEXs.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.
Humans ; Transcriptional Activation ; RNA, Guide, CRISPR-Cas Systems ; Gene Expression Regulation ; CRISPR-Cas Systems/genetics*

Objective:To investigate the risk factors and treatment outcome of persistent inflammation-immunosuppression-catabolism syndrome (PICS) in patients with extensive burns.Methods:A retrospective case series study was conducted. From January 2017 to December 2021, 220 patients with extensive burns who were admitted to Guangzhou Red Cross Hospital of Jinan University met the inclusion criteria, including 168 males and 52 females, aged 18-84 (43±14) years. According to the occurrence of PICS, the patients were divided into PICS group (84 patients) and non-PICS group (136 patients). The general data such as sex, age, complication of underlying diseases and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score on admission, sepsis-related organ failure evaluation (SOFA) scores on admission and 14 days post admission, and proportion of patients with mechanical ventilation over 48 h during treatment, special conditions such as total burn area, full-thickness burn area, proportion of patients admitted within 48 h post injury, and exposed deep wound area at the 30 th day post injury, outcome indicators such as hospitalization day, total cost of hospital stay, number of surgeries, and death of patients in the 2 groups were collected and analyzed. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. The multivariate logistic regression analysis was performed on the indicators with statistically significant differences between the two groups except for outcome indicators, and the independent risk factors influencing secondary PICS in patients with extensive burns were screened. Results:The APACHE Ⅱ and SOFA scores on admission, and proportion of patients with mechanical ventilation over 48 h during treatment of patients in PICS group were significantly higher than those in non-PICS group ( t=6.78, Z=-4.75, χ2=4.74, respectively, P<0.05). There were no statistically significant differences in the rest of general data of patients between the two groups ( P>0.05). The total burn area, full-thickness burn area, and exposed deep wound area at the 30 th day post injury in PICS group were significantly greater than those in non-PICS group ( t=6.29, Z=-7.25, Z=-8.73, P<0.05), the exposed deep wound areas at the 30 th day post injury in PICS group and non-PICS group were respectively 25% (15%, 35%) total body surface area (TBSA) and 8% (0, 13%) TBSA, while the proportion of patients admitted within 48 h post injury was significantly lower than that in non-PICS group ( χ2=6.13, P<0.05). The hospitalization day, total cost of hospital stay, and number of surgeries of patients in PICS group were significantly higher than those in non-PICS group (with Z values of -7.12, -8.48, and -6.87, respectively, P<0.05), while the deaths of patients in the 2 groups were similar ( P>0.05). The APACHE Ⅱ score on admission and exposed deep wound area at the 30 th day post injury both were the independent risk factors for PICS in patients with extensive burns (with odds ratios of 1.15 and 1.07, 95% confidence intervals of 1.06-1.25 and 1.05-1.10, respectively, P<0.05). Conclusions:The APACHE Ⅱ score on admission and exposed deep wound area at the 30 th day post injury are the independent risk factors for PICS in patients with extensive burns. The patients with secondary PICS had good prognosis with more surgical intervention and hospitalization day, and higher total cost of hospital stay.

Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.

Objective:To observe the changes of macular morphology and blood flow after minimally invasive vitrectomy (PPV) in patients with severe non-proliferative diabetic retinopathy (sNPDR).Methods:A prospective clinical study. From January 2020 to April 2021, 17 consecutive sNPDR patients with 17 eyes who were diagnosed and received PPV treatment at the Zhongshan Ophthalmic Center of Sun Yat-sen University were included in the study. There were 12 males with 12 eyes and 5 females with 5 eyes; the average age was 55 years old; the average duration of diabetes was 11 years; the average glycosylated hemoglobin was 7.9%. Before the operation and 1, 3, and 6 months after the operation, all the affected eyes underwent best corrected visual acuity (BCVA), standard 7-field fundus color photography, and optical coherence tomography angiography (OCTA). An OCTA instrument was used to scan the macular area of the affected eye with in the range of 3 mm×3 mm to measure the central subfoveal thickness (CST), the thickness of the ganglion cell complex (GCC) in the macular area, the thickness of the retinal nerve fiber layer (RNFL), and the superficial capillary plexus (SCP) vessel density and perfusion density in the macular area, macular avascular zone (FAZ) area, a-circularity index (AI). Before the operation and 6 months after the operation, the least significant difference test was used for the pairwise comparison.Results:Before the operation, 1, 3, and 6 months after the operation, the FAZ area of the macular area were 0.34±0.14, 0.35±0.10, 0.37±0.10, 0.36±0.13 mm 2, respectively; AI were 0.52±0.13, 0.54±0.11, 0.57±0.10, 0.60±0.11; CST was 282.6±66.7, 290.4±70.9, 287.2±67.5, 273.2± 49.6 μm; GCC thickness were 77.1±15.5, 74.3±13.9, 72.6±16.2, 78.5±18.3 μm; the thickness of RNFL was 97.9±13.8, 101.3±14.6, 97.7±12.0, 96.1±11.4 μm, respectively. The overall blood flow density of SCP in the macula were (16.79±1.43)%, (16.71±1.82)%, (17.30±2.25)%, (17.35±1.22)%; the overall perfusion density were 0.32±0.02, 0.32±0.03, 0.33±0.03, 0.33±0.02, respectively. After the operation, the CST increased first and then decreased; the thickness of RNFL increased 1 month after the operation, and then gradually decreased. Comparison of the parameters before and 6 months after the operation showed that the AI improved, and the difference was statistically significant ( P=0.049); the difference in FAZ area and the thickness of CST, GCC, and RNFL was not statistically significant ( P=0.600, 0.694, 0.802, 0.712); There was no statistically significant difference in the retina SCP blood flow density and perfusion density in the macular area ( P=0.347, 0.361). Conclusion:Compared with before surgery, there is no significant change in macular structure and blood flow density in sNPDR patients within 6 months after minimally invasive PPV.

Mycobacterium tuberculosis (MTB) utilizes multiple mechanisms to obtain antibiotic resistance during the treatment of infections. In addition, the biofilms, secreted by MTB, can further protect the latter from the contact with drug molecules and immune cells. These self-defending mechanisms lay a formidable challenge to develop effective therapeutic agents against chronic and recurring antibiotic-tolerant MTB infections. Although several inexpensive and effective drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) have been discovered for the treatment regimen, MTB continues to cause considerable morbidity and mortality worldwide. Antibiotic resistance and tolerance remain major global issues, and innovative therapeutic strategies are urgently needed to address the challenges associated with pathogenic bacteria. Gratifyingly, the cell wall synthesis of tubercle bacilli requires the participation of many enzymes which exclusively exist in prokaryotic organisms. These enzymes, absent in human hepatocytes, are recognized as promising targets to develop anti-tuberculosis drug. In this paper, we discussed the critical roles of potential drug targets in regulating cell wall synthesis of MTB. And also, we systematically reviewed the advanced development of novel bioactive compounds or drug leads for inhibition of cell wall synthesis, including their discovery, chemical modification, in vitro and in vivo evaluation.