Robust and efficient control of therapeutic gene expression is needed for timing and dosing of gene therapy drugs in clinical applications. Ribozyme riboswitch provides a promising building block for ligand-controlled gene-regulatory system, based on its property that exhibits tunable gene regulation, design modularity, and target specificity. Ribozyme riboswitch can be used in various gene delivery vectors. In recent years, there have been breakthroughs in extending ribozyme riboswitch's application from gene-expression control to cellular function and fate control. High throughput screening platforms were established, that allow not only rapid optimization of ribozyme riboswitch in a microbial host, but also straightforward transfer of selected devices exhibiting desired activities to mammalian cell lines in a predictable manner. Mathematical models were employed successfully to explore the performance of ribozyme riboswitch quantitively and its rational design predictably. However, to progress toward gene therapy relevant applications, both precision rational design of regulatory circuits and the biocompatibility of regulatory ligand are still of crucial importance.

Objective:To explore the clinical effect of repairing the ankle soft tissue defects with bone exposure using descending branch of lateral circumflex femoral artery (LCFA-db) perforator flap.Methods:From May 2014 to March 2018, 11 patients with ankle soft tissue defect with bone and tendon exposure were treated in the First Central Hospital of Baoding City ( 9 males and 2 females, aged from 19 to 47 years). VSD treatment was performed after debridement. When the wound show no signs of infection, the secondary repair was performed using the LCFA-db perforator flap. The area of the flap was 6.5 cm×4.5 cm-16.5 cm×8.5 cm. Followed-up was acquired to be used for evaluating the clinical effect.Results:There were no complications such as vasospasm or vascular crisis for transplanted flap after surgery. In 11 cases, 2 cases had necrosis of 0.5-1.0 cm in the distal part of the flap. Both were completely healed after dressing and related treatment. The flaps in the rest of patients survived successfully. The patients were followed up for 4-16 months with a mean time of 10.4 months. These flaps survived with good appearance, no swelling, no need for secondary surgery, soft texture, abrasion resistant and no pigmentation. Protective sense was restored. At the last follow-up, the American Orthopedic Foot and Ankle Society Score (AOFAS) score was ranging from 74 to 98 in 11 cases with the average score of 90.55. The outcomes were excellent in 8 cases, good in 2 cases and fair in 1 case. The donor site of the flap healed well. The flexion and extension of knee joint were normal with the good appearance and no impaired function.Conclusions:LCFA-db perforator flap may serve as an alternative option for reconstructing the ankle with soft-tissue defect.

Objective:To explore the clinical effect of repairing the ankle soft tissue defects with bone exposure using descending branch of lateral circumflex femoral artery (LCFA-db) perforator flap.Methods:From May 2014 to March 2018, 11 patients with ankle soft tissue defect with bone and tendon exposure were treated in the First Central Hospital of Baoding City ( 9 males and 2 females, aged from 19 to 47 years). VSD treatment was performed after debridement. When the wound show no signs of infection, the secondary repair was performed using the LCFA-db perforator flap. The area of the flap was 6.5 cm×4.5 cm-16.5 cm×8.5 cm. Followed-up was acquired to be used for evaluating the clinical effect.Results:There were no complications such as vasospasm or vascular crisis for transplanted flap after surgery. In 11 cases, 2 cases had necrosis of 0.5-1.0 cm in the distal part of the flap. Both were completely healed after dressing and related treatment. The flaps in the rest of patients survived successfully. The patients were followed up for 4-16 months with a mean time of 10.4 months. These flaps survived with good appearance, no swelling, no need for secondary surgery, soft texture, abrasion resistant and no pigmentation. Protective sense was restored. At the last follow-up, the American Orthopedic Foot and Ankle Society Score (AOFAS) score was ranging from 74 to 98 in 11 cases with the average score of 90.55. The outcomes were excellent in 8 cases, good in 2 cases and fair in 1 case. The donor site of the flap healed well. The flexion and extension of knee joint were normal with the good appearance and no impaired function.Conclusions:LCFA-db perforator flap may serve as an alternative option for reconstructing the ankle with soft-tissue defect.

【Objective】 To investigate the risk factors of red blood cell transfusion frequency (fRBCT) toward newborns with very/extremely low birth weight (V/ELBW) who experienced <32 weeks of gestational age and were complicated with neonatal respiratory distress syndrome (NRDS), and to explore related complications and predictive indicators that can arise from increased fRBCT, so as to provide safe and scientific blood transfusion recommendations for children with NRDS. 【Methods】 A total of 585 cases of V/ELBW NRDS newborns who experienced <32 weeks of gestational age between January 2016 and December 2020 were retrospectively collected. They were divided into three groups according to the fRBCT throughout their hospitalization[fRBCT = 0(n = 97), 1 ≤fRBCT≤2(n = 253), and fRBCT≥3(n= 235) ]. Clinical data and laboratory parameters of all three groups were compared to identify the risk factors of increased blood transfusion frequency toward V/ELBW NRDS newborns. 【Results】 Statistically significant differences in gestational age (week) (30.72±1.84 vs 29.87±1.66 vs 28.29±1.46), birth weight(g) (1 366.19± 128.12 vs 1 265.20± 163.98 vs 1 081.73± 196.06), hemoglobin level(g/L) (172.37±19.98 vs 161.96±21.41 vs 154.33±24.61) and hematocrit ratio(%) (50.46±5.74 vs 47.69±5.55 vs 45.46±6.84) at admission, as well as duration of hospital stay(d) (40 vs 51 vs 68), non-invasive ventilation(d) (6 vs 11.01 vs 24.56) and intravenous nutrition (IVN) (d) (16.73 vs 22.37 vs 30.74) were found among all three groups (all P<0.05) . Duration of invasive ventilation in Group fRBCT ≥3 (7.66 days) were significantly higher than those in Group fRBCT = 0 and Group 1 ≤fRBCT≤2, showing statistically significant differences (P<0.05). Pairwise comparison of the incidences of hematosepsis (1%, 1/97 vs 4%, 10/253 vs 9.4%, 22/235 ), retinopathy of prematurity (ROP) (16.5%, 16/97 vs 17%, 43/253 vs 46.8%, 110/235) and bronchopulmonary dysplasia (BPD) (4.1%, 4/97 vs 19%, 48/253 vs 59.1%, 139/235) among the three groups demonstrated statistically significant differences (P<0.05). The incidence of neonatal necrotizing enterocolitis (NEC) in Group fRBCT≥3 (26.8%, 63/235) also showed statistically significant differences in relation to Group fRBCT = 0 (P<0.05). Multivariate logistic regression analysis also proved that duration of hospital stay, invasive ventilation and IVN were independent risk factors for Group fRBCT≥ 3 (OR= 1.048, 1.073, and 1.030; all P<0.05). The receiver operating characteristic (ROC) curves indicated that duration of hospital stay, invasive ventilation and IVN made better predictors for Group fRBCT≥3. Areas under the ROC curves were 0.841, 0.766 and 0.716, while the corresponding cutoff values were respectively >57 days, >2.75 days and >23.75 days. 【Conclusion】 Increased fRBCT may complicate V/ELBW NRDS newborns who experienced <32 weeks of gestational age with NEC, hematosepsis, BPD and ROP. Duration of hospital stay, invasive ventilation and IVN are relatively effective predictive indicators for whether such cases have undergone ≥3 red blood cell transfusions throughout their hospitalization.

Objective To investigate the efficacy of transcranial direct current stimulation(tDCS)on sleep disorder in patients with Parkinson's disease(PD).Methods From July 2021 to July 2023,patients with PD and sleep disorders in the Department of Neurosurgery of the Second People's Hospital of Guangdong Province were selected.The enrolled patients were divided into sham stimulation group(n=28)and true stimulation group(tDCS)(n=29)according to the inclusion and exclusion criteria.MDS-UPDRS,PDSS and other rating scales were used to evaluate the patients.Before and after tDCS treatment,MS-11 was used for intelligent sleep monitor-ing.The baseline and improvement of sleep disorders in the two groups before and after treatment were analyzed.Results Before tDCS treatment,there was no significant difference in general conditions and scale scores between the two groups(P＞0.05).There was no significant difference in polysomnographic monitoring results between the two groups before treatment(P＞0.05).Compared with pre-treatment,there was no significant difference in sleep monitoring results in the sham stimulation group(P＞0.05),while the sleep duration and sleep efficiency signifi-cantly increased,the nighttime awakening duration,nighttime awakening frequency,MDS-UPDRS-Ⅲ score,and LEDD dose significantly decreased in the true stimulation group,with statistical significance(P＜0.05).Conclusion Pharmacological treatment combined with tDCS treatment is effective for sleep disorders and motor function in patients with PD,which could increase the sleep duration and sleep efficiency of PD patients with sleep disorders to a certain extent,reduce the nighttime awakening duration and frequency,thereby improving the fatigue symp-toms during the daytime,and improving the efficacy of conventional pharmacological treatment for PD.

Objective:To analyze the hemodynamic changes of different types of unruptured intracranial aneurysms before and after flow diverter (FD) treatment with computational fluid dynamics (CFD), and lay research foundation for precision treatment and prognosis evaluation for unruptured intracranial aneurysms.Methods:Four patients with different types of unruptured intracranial aneurysms, admitted to Department of Neurosurgery, First Affiliated Hospital of Air Force Medical University from January 2022 to March 2022, were chosen. Digital subtraction angiography (DSA) data of the patients before and immediately after surgery were collected. Morphological and hemodynamic parameters of the aneurysms were calculated by 3D reconstruction, finite element simulation, and CFD methods: ostium ratio (OsR), neck ratio (NR), area ratio (ArR), volume ratio (VoR), wall shear stress (WSS), normalized wall shell stress (NWSS), blood inflow, relative inflow, aneurysm average velocity, parent artery average velocity, normalized velocity, residual flow volume (RFV), and inflow concentration index (ICI); differences of these indexes before and after treatment were compared.Results:The OsR of 6 aneurysms was 0.225, 0.267, 0.265, 0.389, 1.000, 1.000, respectively; NR was 1.220, 0.274, 1.090, 1.587, 2.809, and 4.019, respectively; ArR was 0.608 and 0.224, 0.623, 3.462, 1.225 and 1.784, respectively; and VoR was 0.386, 0.052, 0.212, 3.462, 0.422 and 1.882, respectively. The parameters of WSS, NWSS, blood inflow, relative inflow, aneurysm average velocity, parent artery average velocity, normalized velocity, RFV, and ICI decreased obviously after FD implantation.Conclusion:On the basis of 3D reconstruction combined with FD/coil virtual implantation, CFD-based hemodynamic analysis can obtain accurate parameters of different types of intracranial aneurysms before and after FD treatment.

ObjectiveTo assess the curative effects of Fangji Huangqi detumescence prescription （FHDP） on synovitis and polarization of synovial macrophages of knee osteoarthritis （KOA） model in rats induced by Hulth method. MethodThirty-six rats were randomly divided into sham operation group， model group， high-dose， medium-dose， and low-dose （29.16， 14.58， and 7.29 g·kg^-1） FHDP groups， and loxoprofen sodium （16.2 mg·kg^-1） group. KOA model in rats was induced by modified Hulth method. Six weeks after the operation， rats were given high， medium， and low concentrations of FHDP， normal saline （NS）， and loxoprofen sodium according to the group to intervene， and sacrificed after 2-week administration. Synovium and cartilage histopathological changes were observed after hematoxylin-eosin （HE） staining. Flow cytometry （FCM） and immunofluorescence （IF） test were used to evaluate the polarization of M1/M2 macrophages. Immunohistochemistry （IMC） and enzyme-linked immunosorbent assay （ELISA） were used to detect the related protein expression levels of macrophage polarization， such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and matrix metalloproteinase-13 （MMP-13） in joint tissues and serum. ResultCompared with the sham operation group， Krenn and Mankin scores in the model group were significantly increased （P<0.01）. Compared with the model group， Krenn score was decreased in all administration groups （P<0.05， P<0.01）， but there was no significant difference in Mankin score in any administration groups. Compared with the sham operation group， M1/mø （CD38⁺） ratio in the model group was significantly increased （P<0.01）， and M2/mø （CD206⁺） ratio in the model group was decreased （P<0.05）. Compared with the model group， M1/mø ratio in the high， medium， and low-dose FHDP groups was decreased （P<0.05， P<0.01）， but M2/mø ratio was increased in all administration groups （the difference had no statistical significance）. Compared with the sham operation group， M1/M2 ratio in the model group was significantly increased （P<0.01）. Compared with the model group， M1/M2 ratio in all FHDP groups was significantly decreased （P<0.01）， and M1/M2 ratio in the high and medium-dose FHDP groups was lower than that in the loxoprofen sodium group （P<0.05）. Compared with the sham operation group， the levels of TNF-α， IL-1β， and MMP-13 in synovium and cartilage of the model group were significantly increased （P<0.01）， the level of IL-10 was significantly decreased （P<0.01）. Compared with the model group， the levels of TNF-α and IL-1β in synovium were decreased in all administration groups （P<0.05）， but the difference of the levels of MMP-13 and IL-10 in synovium had no statistical significance. The level of inflammatory mediators in cartilage was not affected in all administration groups. Compared with the sham operation group， the levels of TNF-α and IL-β in serum of the model group were significantly increased （P<0.01）， the level of IL-10 was decreased （P<0.05）. Compared with the model group， the level of TNF-α in the high-dose FHDP group was decreased （P<0.05）， and the level of IL-10 was increased in all administration groups （P<0.05， P<0.01）. The difference of the level of IL-β in all administration groups had no statistical significance. ConclusionFHDP attenuated the synovitis of KOA rats. FHDP exert the effect on the releasing of proinflammatory cytokines and MMP by inhibiting the polarization of M1 macrophages in synovium， and had no significant effect on the polarization of M2 macrophages. Modulating the imbalanced polarization of synovial macrophages was a possible mechanism of FHDP on attenuating synovitis and treating KOA.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

BACKGROUND: Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. METHODS: From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. RESULTS: (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. CONCLUSIONS Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.
Humans ; COVID-19 ; Retrospective Studies ; Lung Neoplasms/drug therapy* ; Incidence ; Pneumonia/etiology*

Over the past decade, dramatic progress has been made in dental research areas involving laser therapy. The photobiomodulatory effect of laser light regulates the behavior of periodontal tissues and promotes damaged tissues to heal faster. Additionally, photobiomodulation therapy (PBMT), a non-invasive treatment, when applied in orthodontics, contributes to alleviating pain and reducing inflammation induced by orthodontic forces, along with improving tissue healing processes. Moreover, PBMT is attracting more attention as a possible approach to prevent the incidence of orthodontically induced inflammatory root resorption (OIIRR) during orthodontic treatment (OT) due to its capacity to modulate inflammatory, apoptotic, and anti-antioxidant responses. However, a systematic review revealed that PBMT has only a moderate grade of evidence-based effectiveness during orthodontic tooth movement (OTM) in relation to OIIRR, casting doubt on its beneficial effects. In PBMT-assisted orthodontics, delivering sufficient energy to the tooth root to achieve optimal stimulation is challenging due to the exponential attenuation of light penetration in periodontal tissues. The penetration of light to the root surface is another crucial unknown factor. Both the penetration depth and distribution of light in periodontal tissues are unknown. Thus, advanced approaches specific to orthodontic application of PBMT need to be established to overcome these limitations. This review explores possibilities for improving the application and effectiveness of PBMT during OTM. The aim was to investigate the current evidence related to the underlying mechanisms of action of PBMT on various periodontal tissues and cells, with a special focus on immunomodulatory effects during OTM.
Humans ; Inflammation ; Low-Level Light Therapy/adverse effects* ; Orthodontics ; Root Resorption/therapy* ; Tooth Movement Techniques