Minimally invasive surgeries for spontaneous hypertensive intracerebral hemorrhage (MISICH): a multicenter randomized controlled trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is a common stroke type with high morbidity and mortality. There are mainly three surgical methods for treating ICH. Unfortunately, thus far, no specific surgical method has been proven to be the most effective. We carried out this study to investigate whether minimally invasive surgeries with endoscopic surgery or stereotactic aspiration (frameless navigated aspiration) will improve functional outcomes in patients with supratentorial ICH compared with small-bone flap craniotomy. METHODS: In this parallel-group multicenter randomized controlled trial conducted at 16 centers, patients with supratentorial hypertensive ICH were randomized to receive endoscopic surgery, stereotactic aspiration, or craniotomy at a 1:1:1 ratio from July 2016 to June 2022. The follow-up duration was 6 months. Patients were randomized to receive endoscopic evacuation, stereotactic aspiration, or small-bone flap craniotomy. The primary outcome was favorable functional outcome, defined as the proportion of patients who achieved a modified Rankin scale (mRS) score of 0-2 at the 6-month follow-up. RESULTS: A total of 733 patients were randomly allocated to three groups: 243 to the endoscopy group, 247 to the aspiration group, and 243 to the craniotomy group. Finally, 721 patients (239 in the endoscopy group, 246 in the aspiration group, and 236 in the craniotomy group) received treatment and were included in the intention-to-treat analysis. Primary efficacy analysis revealed that 73 of 219 (33.3%) in the endoscopy group, 72 of 220 (32.7%) in the aspiration group, and 47 of 212 (22.2%) in the craniotomy group achieved favorable functional outcome at the 6-month follow-up (P = .017). We got similar results in subgroup analysis of deep hemorrhages, while in lobar hemorrhages the prognostic outcome was similar among three groups. Old age, deep hematoma location, large hematoma volume, low preoperative GCS score, craniotomy, and intracranial infection were associated with greater odds of unfavorable outcomes. The mean hospitalization expenses were ¥92,420 in the endoscopy group, ¥77,351 in the aspiration group, and ¥100,947 in the craniotomy group (P = .000). CONCLUSIONS: Compared with small bone flap craniotomy, endoscopic surgery and stereotactic aspiration improved the long-term outcome of hypertensive ICH, especially deep hemorrhages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811614.

Remaining Useful Life Prediction Based on Deep Learning: A Survey.

Remaining useful life (RUL) is a metric of health state for essential equipment. It plays a significant role in health management. However, RUL is often random and unknown. One type of physics-based method builds a mathematical model for RUL using prior principles, but this is a tough task in real-world applications. Another type of method estimates RUL from available information through condition and health monitoring; this is known as the data-driven method. Traditional data-driven methods require significant human effort in designing health features to represent performance degradation, yet the prediction accuracy is limited. With breakthroughs in various application scenarios in recent years, deep learning techniques provide new insights into this problem. Over the past few years, deep-learning-based RUL prediction has attracted increasing attention from the academic community. Therefore, it is necessary to conduct a survey on deep-learning-based RUL prediction. To ensure a comprehensive survey, the literature is reviewed from three dimensions. Firstly, a unified framework is proposed for deep-learning-based RUL prediction and the models and approaches in the literature are reviewed under this framework. Secondly, detailed estimation processes are compared from the perspective of different deep learning models. Thirdly, the literature is examined from the perspective of specific problems, such as scenarios where the collected data consist of limited labeled data. Finally, the main challenges and future directions are summarized.

Overexpression of USP22 ameliorates LPS-induced endometrial stromal cells inflammation and modulates cells decidualization by inhibiting ferroptosis.

Endometritis and the failure of decidualization of the endometrium are important factors contributing to the increased incidence of abortion. USP22 is associated with various inflammatory diseases and has been shown to be involved in endometrial decidualization in mice. This study aims to investigate whether USP22 is involved in the regulation of inflammatory response and decidualization in human endometrial stromal cells (hESCs). In this study, lipopolysaccharide (LPS) was used to induce inflammation in hESCs, and MPA combined with cAMP was used to induce decidualization of hESCs. USP22 overexpression vector was constructed to study the role of USP22 in endometritis. The results showed that the USP22 protein and mRNA levels were decreased in LPS-induced hESCs. LPS induction increased the levels of TNF-α, IL-1ß, and IL-6, as well as the expression of iNOS and COX2 proteins in hESCs. In the LPS group, the levels of F-actin, PRL, IGFBP1, SLC7A11, and GPX4 proteins decreased, while the levels of lipid peroxidation and total iron content increased. Additionally, the levels of ACSL4 and TFR1 proteins were up-regulated. Overexpression of USP22 reversed LPS-induced cellular inflammation, attenuated decidualization, and inhibited ferroptosis. However, the use of ferroptosis inducers diminished the regulatory effects of USP22 on inflammatory responses and decidualization. In summary, these suggested that USP22 reduces the LPS-induced inflammatory response and regulates the decidualization of hESCs, and possibly involving ferroptosis.

Head model dataset for mixed reality navigation in neurosurgical interventions for intracranial lesions.

Mixed reality navigation (MRN) technology is emerging as an increasingly significant and interesting topic in neurosurgery. MRN enables neurosurgeons to "see through" the head with an interactive, hybrid visualization environment that merges virtual- and physical-world elements. Offering immersive, intuitive, and reliable guidance for preoperative and intraoperative intervention of intracranial lesions, MRN showcases its potential as an economically efficient and user-friendly alternative to standard neuronavigation systems. However, the clinical research and development of MRN systems present challenges: recruiting a sufficient number of patients within a limited timeframe is difficult, and acquiring low-cost, commercially available, medically significant head phantoms is equally challenging. To accelerate the development of novel MRN systems and surmount these obstacles, the study presents a dataset designed for MRN system development and testing in neurosurgery. It includes CT and MRI data from 19 patients with intracranial lesions and derived 3D models of anatomical structures and validation references. The models are available in Wavefront object (OBJ) and Stereolithography (STL) formats, supporting the creation and assessment of neurosurgical MRN applications.

Catalytic 1,1-diazidation of alkenes.

Compared to well-developed catalytic 1,2-diazidation of alkenes to produce vicinal diazides, the corresponding catalytic 1,1-diazidation of alkenes to yield geminal diazides has not been realized. Here we report an efficient approach for catalytic 1,1-diazidation of alkenes by redox-active selenium catalysis. Under mild conditions, electron-rich aryl alkenes with Z or E or Z/E mixed configuration can undergo migratory 1,1-diazidation to give a series of functionalized monoalkyl or dialkyl geminal diazides that are difficult to access by other methods. The method is also effective for the construction of polydiazides. The formed diazides are relatively safe by TGA-DSC analysis and impact sensitivity tests, and can be easily converted into various valuable molecules. In addition, interesting reactivity that geminal diazides give valuable molecules via the geminal diazidomethyl moiety as a formal leaving group in the presence of Lewis acid is disclosed. Mechanistic studies revealed that a selenenylation-deselenenylation followed by 1,2-aryl migration process is involved in the reactions, which provides a basis for the design of new reactions.

Comparison of water-soluble organic matter (WSOM)-containing and WSOM-free biochars for simultaneous sorption of lead and cadmium.

The effects of individual biochar constituents and natural environmental media on the immobilization behaviors and chemical activities of toxic heavy metals are still poorly understood. In this work, the physicochemical properties of raw corn straw (CS) and CS-derived biochar materials as well as their sorption abilities and retention mechanisms for lead (Pb) and cadmium (Cd) were evaluated by combining batch experiments and spectral approaches. According to the spectral analysis results and single variable principle, the setting of biochars after soaking in solution as the control group was suggested when evaluating their retention mechanisms for Pb and Cd. The rising of ionic strength did not apparently affect the immobilization of Pb by biochar prepared at 500 °C (i.e., CB500) and Pb/Cd by water-soluble organic matter (WSOM)-free CB500 (i.e., DCB500), while slightly inhibited the sorption of Cd by CB500. Pb and Cd exhibited a mutual inhibition effect on their sorption trends with a higher sorption preference of Pb. The dominant fixation mechanism of Pb by CB500 and DCB500 was identified to be mineral precipitation. In contrast, the main sorption mechanism of Cd changed from mineral precipitation in the single-metal system to surface complexation in the binary-metal system. The sorption ratios of Pb and Cd on CB500 were comparable to those on DCB500 with the coexistence of mixed natural organic matters (NOM) and ferrihydrite. The current experimental findings suggested that DCB500 was a suitable remediation agent for regulating the migration behaviors of toxic Pb and Cd in acidic and NOM-rich soil and water systems.

A patient-specific, interactive, multiuser, online mixed-reality neurosurgical training and planning system.

OBJECTIVE: Mixed-reality simulation is an emerging tool for creating anatomical models for preoperative planning. Its use in neurosurgical training (NT) has been limited because of the difficulty in real-time interactive teaching. This study describes the development of a patient-specific, interactive mixed-reality NT system. The authors took cases of intracranial tumor resection or neurovascular compression (NVC) as examples to verify the technical feasibility and efficacy of the mixed-reality NT system for residents' training and preoperative planning. METHODS: This study prospectively enrolled 40 patients who suffered from trigeminal neuralgia, hemifacial spasms, or intracranial tumors. The authors used a series of software programs to process the multimodal imaging data, followed by uploading the holographic models online. They used a HoloLens or a standard iOS device to download and display the holographic models for training. Ten neurosurgical residents with different levels of surgical experience were trained with this mixed-reality NT system. Change in surgical strategy was recorded, and a questionnaire survey was conducted to evaluate the efficacy of the mixed-reality NT system. RESULTS: The system allows the trainer and trainee to view the mixed-reality model with either a HoloLens or an iPad/iPhone simultaneously online at different locations. Interactive manipulation and instant updates were able to be achieved during training. A clinical efficacy validation test was conducted. The surgeons changed their exploration strategy in 48.3% of the NVC cases. For residents with limited experience in surgery, the exploration strategy for 75.0% of all patients with NVC was changed after the residents were trained with the mixed-reality NT system. Of the 60 responses for intracranial tumors, the trainee changed the surgical posture in 19 (31.7%) cases. The change of the location (p = 0.0338) and size (p = 0.0056) of craniotomy are significantly related to the experience of the neurosurgeons. CONCLUSIONS: The mixed-reality NT system is available for local or real-time remote neurosurgical resident training. It may effectively help neurosurgeons in patient-specific training and planning of surgery for cases of NVC and intracranial tumor. The authors expect the system to have a broader application in neurosurgery in the near future.

A Novel Registration Method for a Mixed Reality Navigation System Based on a Laser Crosshair Simulator: A Technical Note.

Mixed Reality Navigation (MRN) is pivotal in augmented reality-assisted intelligent neurosurgical interventions. However, existing MRN registration methods face challenges in concurrently achieving low user dependency, high accuracy, and clinical applicability. This study proposes and evaluates a novel registration method based on a laser crosshair simulator, evaluating its feasibility and accuracy. A novel registration method employing a laser crosshair simulator was introduced, designed to replicate the scanner frame's position on the patient. The system autonomously calculates the transformation, mapping coordinates from the tracking space to the reference image space. A mathematical model and workflow for registration were designed, and a Universal Windows Platform (UWP) application was developed on HoloLens-2. Finally, a head phantom was used to measure the system's target registration error (TRE). The proposed method was successfully implemented, obviating the need for user interactions with virtual objects during the registration process. Regarding accuracy, the average deviation was 3.7 ± 1.7 mm. This method shows encouraging results in efficiency and intuitiveness and marks a valuable advancement in low-cost, easy-to-use MRN systems. The potential for enhancing accuracy and adaptability in intervention procedures positions this approach as promising for improving surgical outcomes.

Application of DKI and IVIM imaging in evaluating histologic grades and clinical stages of clear cell renal cell carcinoma.

Purpose: To evaluate the value of quantitative parameters derived from diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) in differentiating histologic grades and clinical stages of clear cell renal cell carcinoma (ccRCC). Materials and methods: A total of 65 patients who were surgically and pathologically diagnosed as ccRCC were recruited in this study. In addition to routine renal magnetic resonance imaging examination, all patients underwent preoperative IVIM and DKI. The corresponding diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean diffusivity (MD), kurtosis anisotropy (KA), and mean kurtosis (MK) values were obtained. Independent-samples t-test or Mann-Whitney U test was used for comparing the differences in IVIM and DKI parameters among different histologic grades and clinical stages. The diagnostic efficacy of IVIM and DKI parameters was evaluated using the receiver operating characteristic (ROC) curve. Spearman's correlation analysis was used to separately analyze the correlation of each parameter with histologic grades and stages of ccRCC. Results: The D and MD values were significantly higher in low-grade ccRCC than high-grade ccRCC (all p < 0.001) and in low-stage than high-stage ccRCC (all p < 0.05), and the f value of high-stage ccRCC was lower than that of low-stage ccRCC (p = 0.007). The KA and MK values were significantly higher in low-grade than high-grade ccRCC (p = 0.000 and 0.000, respectively) and in low-stage than high-stage ccRCC (p = 0.000 and 0.000, respectively). The area under the curve (AUC) values of D, D*, f, MD, KA, MK, DKI, and IVIM+DKI values were 0.825, 0.598, 0.626, 0.792, 0.750, 0.754, 0.803, and 0.857, respectively, in grading ccRCC and 0.837, 0.719, 0.710, 0.787, 0.796, 0.784, 0.864, 0.823, and 0.916, respectively, in staging ccRCC. The AUC of IVIM was 0.913 in staging ccRCC. The D, D*, and MD values were negatively correlated with the histologic grades and clinical stages (all p < 0.05), and the KA and MK values showed a positive correlation with histologic grades and clinical stages (all p < 0.05). The f value was also negatively correlated with the ccRCC clinical stage (p = 0.008). Conclusion: Both the IVIM and DKI values can be used preoperatively to predict the degree of histologic grades and stages in ccRCC, and the D and MD values have better diagnostic performance in the grading and staging. Also, further slightly enhanced diagnostic efficacy was observed in the model with combined IVIM and DKI parameters.

Intraventricular SEEG and laser ablation for the treatment of infantile spasm: Technical note.

OBJECTIVES: Infantile spasm (IS) is an epileptic encephalopathy with ongoing neurological damage due to seizures and epileptiform abnormalities. Epilepsy surgery is considered for children refractory to drug therapy, especially when there is a focal brain lesion. In this study, we investigated the feasibility and efficacy of intraventricular stereotactic electroencephalography (SEEG) and laser ablation for the treatment of IS children with focal brain lesions. METHODS: We performed the first reported study using ventriculoscopic laser ablation to treat IS. Seven IS children with drug-resistant epilepsy and definite encephalomalacia on brain magnetic resonance imaging scan were included in this study. Ablation was performed after confirmation of epileptiform discharges by SEEG under the surveillance of ventriculoscope. RESULTS: The median follow-up time for the cohort was 3.1 years and 86% (6/7) of the children had an Engel class ≤III epilepsy at the final follow-up. Five (71%) children had a reduction in seizure medication usage, and the other two were on the same amount as preablation. None of the children experienced serious new neurological deficits. Laser ablation might result in seizure freedom by destroying the local brain network and blocking the spread of abnormal discharges. CONCLUSIONS: Intraventricular SEEG and laser ablation was feasible and effective for the treatment of IS. Further studies are warranted.

Establishment and optimization of an in vitro guinea pig oocyte maturation system.

Guinea pigs are a valuable animal model for studying various diseases, including reproductive diseases. However, techniques for generating embryos via embryo engineering in guinea pigs are limited; for instance, in vitro maturation (IVM) technique is preliminary for guinea pig oocytes. In this study, we aimed to establish and optimize an IVM method for guinea pig oocytes by investigating various factors, such as superovulation induced by different hormones, culture supplementation (e.g., amino acids, hormone, and inhibitors), culture conditions (e.g., oocyte type, culture medium type, and treatment time), and in vivo hCG stimulation. We found that oocytes collected from guinea pigs with superovulation induced by hMG have a higher IVM rate compared to those collected from natural cycling individuals. Moreover, we found that addition of L-cysteine, cystine, and ROS in the culture medium can increase the IVM rate. In addition, we demonstrated that in vivo stimulation with hCG for 3-8 h can further increase the IVM rate. As a result, the overall IVM rate of guinea pig oocytes under our optimized conditions can reach ~69%, and the mature oocytes have high GSH levels and normal morphology. In summary, we established an effective IVM method for guinea pig oocytes by optimizing various factors and conditions, which provides a basis for embryo engineering using guinea pigs as a model.

Deep Learning Techniques in Intelligent Fault Diagnosis and Prognosis for Industrial Systems: A Review.

Fault diagnosis and prognosis (FDP) tries to recognize and locate the faults from the captured sensory data, and also predict their failures in advance, which can greatly help to take appropriate actions for maintenance and avoid serious consequences in industrial systems. In recent years, deep learning methods are being widely introduced into FDP due to the powerful feature representation ability, and its rapid development is bringing new opportunities to the promotion of FDP. In order to facilitate the related research, we give a summary of recent advances in deep learning techniques for industrial FDP in this paper. Related concepts and formulations of FDP are firstly given. Seven commonly used deep learning architectures, especially the emerging generative adversarial network, transformer, and graph neural network, are reviewed. Finally, we give insights into the challenges in current applications of deep learning-based methods from four different aspects of imbalanced data, compound fault types, multimodal data fusion, and edge device implementation, and provide possible solutions, respectively. This paper tries to give a comprehensive guideline for further research into the problem of intelligent industrial FDP for the community.

Hyperhomocysteinemia increases the risk of vertebrobasilar dissecting aneurysm among the male Han Chinese population: a retrospective case-control study.

OBJECT: Vertebrobasilar dissecting aneurysms (VBDAs) are known to have a poor natural history with high rates of re-bleeding and mortality. There is a strong relation between hyperhomocysteinemia (HHcy) and cerebrovascular disease; we perform a retrospective study within the male of Chinese Han population to explore the association between HHcy and VBDAs. METHODS: Eighty-eight male patients with VBDA and Eighty-one male control subjects were evaluated for their serum total homocysteine levels. With multiple logistic regression analysis, the association between HHcy and the risk of VBDAs was estimated. Interaction and stratified analyses were conducted according to age, BMI, smoking status, drinking status, and chronic disease histories. The two-piecewise linear regression model examined the threshold effect. RESULTS: The multivariate logistic regression analyses revealed a significant association between HHcy and VBDAs (odds ratio (OR) = 2.62; 95% confidence interval (CI), 1.02-6.71) after adjusting for classical vascular risk factors. The relationship was stable in all subgroup analysis. The interactive role was not found in the association between HHcy and VBDAs for the potential risk factor. CONCLUSIONS: In summary, our study provides evidence that HHcy can increases the risk of VBDAs in the male Han Chinese population. Further researches with appropriate study designs including sex differences and aneurysm types are needed to verify this association.

Comparison of left ventricular global and segmental strain parameters by cardiovascular magnetic resonance tissue tracking in light-chain cardiac amyloidosis and hypertrophic cardiomyopathy.

Background: Apical sparing of left ventricular (LV) strain can occur in light-chain cardiac amyloidosis (AL-CA). We employed indicators of the strain ratio of the apex to base (RAB) and the relative apical sparing of strain (RAS) on the basis of LV global and segmental strain to distinguish AL-CA from hypertrophic cardiomyopathy (HCM). Methods: In all, 36 AL-CA patients, 37 HCM patients, and 36 healthy controls underwent 3.0 T cardiac magnetic resonance (CMR) examination. We compared LV strain parameters from CMR tissue tracking (CMR-TT), including global and segmental peak radial strain (PRS), peak circumferential strain (PCS), and peak longitudinal strain (PLS); the peak systolic strain rate in radial, circumferential, and longitudinal directions (PSSR_R, PSSR_C, PSSR_L); and the peak diastolic strain rate in radial, circumferential, and longitudinal directions (PDSR_R, PDSR_C, PDSR_L). We also assessed the values of RAB and RAS. Differences in all groups were compared using an independent t-test and a nonparametric rank sum test. Results: In the comparison of global strain parameters, all the peak strain, systolic, and diastolic peak strain rates of the AL-CA group significantly decreased compared with those of the HCM and healthy control groups (all P<0.001). The values of PSSR in all directions were lower in the AL-CA than in the HCM patients (PSSR_R, P<0.001; PSSR_C, P=0.004; PSSR_L, P=0.010) . In the analysis of segmental strain parameters, all peak strains in the basal segment showed significant differences between the AL-CA and HCM groups (all P<0.001). Some strain rate parameters in the basal segment were also noted to be significantly different (PSSR_R, P<0.001; PSSR_L, P<0.001; PDSR_R, P=0.015; PDSR_C, P=0.020). Both the RAB and RAS of peak strain in all directions showed significant differences between the AL-CA and HCM groups (all P<0.001). The RAB of the radial and circumferential PSSR showed statistical differences between the 2 groups (P<0.001 and P=0.001). The RAS in the radial direction of both the PSSR and PDSR was statistically different (P=0.003 and P=0.012). Conclusions: The CMR-TT technique can be used to quantitatively compare global and segmental strain differences between AL-CA and HCM. In addition, RAB and RAS are reliable parameters for assessing the apical sparing pattern and thus, for distinguishing AL-CA from HCM.

Diagnosis of pelvic endometriosis: a preliminary study on the added value of R2*MFGRE sequence in magnetic resonance imaging.

BACKGROUND: Identifying and locating endometriotic lesions is crucial for preoperative planning, so new magnetic resonance imaging (MRI) techniques are urgently needed to improve the diagnostic sensitivity for pelvic endometriosis. PURPOSE: To evaluate the feasibility of R2* multiple fast gradient recalled echo (MFGRE) imaging in the diagnosis of pelvic endometriosis. MATERIAL AND METHODS: A total of 46 patients with suspected endometriosis underwent routine pelvic MRI and R2*MFGRE imaging. Clinical diagnosis was pathologically confirmed one month after MRI examination. Three radiologists who were blinded to the pathological results evaluated the number of ovarian endometriomas (OMAs) and deep infiltrating endometriosis (DIE) lesions using routine MRI and its combination with R2*MFGRE. The diagnostic sensitivity for OMA or DIE using the two examination methods was determined. Two-correlation sample rank-sum tests were used to compare both methods. Additionally, for all lesions, the R2* values were measured and statistically analyzed. RESULTS: Among 46 patients, 47 OMAs and 30 DIE lesions were found surgically and pathologically confirmed. The diagnostic sensitivity of the routine MRI was 87.2% for OMA and 46.7% for DIE. The diagnostic sensitivity of the routine imaging combined with R2*MFGRE was 100% for OMA and 90% for DIE. The two-correlation sample rank-sum test showed a significant difference between both methods (P<0.01, z = -4.26). The median R2* value was 25.20 (IQR=14) for the OMA group, and 45.21 (IQR=40) for the DIE group. The difference between both groups was statistically significant (P<0.01, z = -4.89). CONCLUSION: R2*MFGRE imaging, as a supplement to the routine MRI, could improve the diagnostic sensitivity for pelvic endometriosis, especially for DIE.

Offset-FA: A Uniform Method to Handle Both Unbounded and Bounded Repetitions in Regular Expression Matching.

With the exponential growth of cyber-physical systems (CPSs), security challenges have emerged; attacks on critical infrastructure could result in catastrophic consequences. Intrusion detection is the foundation for CPS security protection, and deep-packet inspection is the primary method for signature-matched mechanisms. This method usually employs regular expression matching (REM) to detect possible threats in the packet payload. State explosion is the critical challenge for REM applications, which originates primarily from features of large character sets with unbounded (closures) or bounded (counting) repetitions. In this work, we propose Offset-FA to handle these repetitions in a uniform mechanism. Offset-FA eliminates state explosion by extracting the repetitions from the nonexplosive string fragments. Then, these fragments are compiled into a fragment-DFA, while a fragment relation table and a reset table are constructed to preserve their connection and offset relationship. To our knowledge, Offset-FA is the first automaton to handle these two kinds of repetitions together with a uniform mechanism. Experiments demonstrate that Offset-FA outperforms state-of-the-art solutions in both space cost and matching speed on the premise of matching correctness, and achieves a comparable matching speed with that of DFA on practical rule sets.

Gene therapy for cystic fibrosis: Challenges and prospects.

Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects.

An examination of the protective effects and molecular mechanisms of curcumin, a polyphenol curcuminoid in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and is an enormous burden on both patients and society. There is an urgent need for effective alternative therapeutic strategies for the treatment of DN, as medical treatment is currently limited. The anti-inflammatory, antioxidative, anti-apoptotic, and anti-fibrosis properties of curcumin, a polyphenol curcuminoid, have been demonstrated in research on diabetic nephropathy. The clinical and preclinical trials and mechanisms by which curcumin affects DN have been discussed in this review. A deeper understanding of the pharmacological effects of curcumin on diabetic nephropathy may provide new therapies to improve the development and occurrence of diabetic nephropathy.

Immunotherapy of targeting MDSCs in tumor microenvironment.

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells which are abnormally accumulated during the differentiation of myeloid cells. Immunosuppression is the main functional feature of MDSCs, which inhibit T cell activity in the tumor microenvironment (TME) and promote tumoral immune escape. The main principle for immunotherapy is to modulate, restore, and remodel the plasticity and potential of immune system to have an effective anti-tumor response. In the TME, MDSCs are major obstacles to cancer immunotherapy through reducing the anti-tumor efficacy and making tumor cells more resistant to immunotherapy. Therefore, targeting MDSCs treatment becomes the priority of relevant studies and provides new immunotherapeutic strategy for cancer treatment. In this review, we mainly discuss the functions and mechanisms of MDSCs as well as their functional changes in the TME. Further, we review therapeutic effects of immunotherapy against MDSCs and potential breakthroughs regarding immunotherapy targeting MDSCs and immune checkpoint blockade (ICB) immunotherapy.

Mobile internet-based mixed-reality interactive telecollaboration system for neurosurgical procedures: technical feasibility and clinical implementation.

OBJECTIVE: To increase access to health interventions and healthcare services for patients in resource-constrained settings, strategies such as telemedicine must be implemented for the allocation of medical resources across geographic boundaries. Telecollaboration is the dominant form of surgical telemedicine. In this study, the authors report and evaluate a novel mobile internet-based mixed-reality interactive telecollaboration (MIMIT) system as a new paradigm for telemedicine and validate its clinical feasibility. METHODS: The application of this system was demonstrated for long-distance, real-time collaboration of neuroendoscopic procedures. The system consists of a local video processing workstation, a head-mounted mixed-reality display device, and a mobile remote device, connected over mobile internet (4G or 5G), allowing global point-to-point communication. Using this system, 20 cases of neuroendoscopic surgery were performed and evaluated. The system setup, composite video latency, technical feasibility, clinical implementation, and future potential business model were analyzed and evaluated. RESULTS: The MIMIT system allows two surgeons to perform complex visual and verbal communication during the operation. The average video delay time is 184.25 msec (range 160-230 msec) with 4G mobile internet, and 23.25 msec (range 20-26 msec) with 5G mobile internet. Excellent image resolution enabled remote neurosurgeons to visualize all critical anatomical structures intraoperatively. Remote instructors could easily make marks on the surgical view; then the composite image, as well as the audio conversation, was transferred to the local surgeon. In this way, a real-time, long-distance collaboration can occur. This system was used for 20 neuroendoscopic surgeries in various cities in China and even across countries (Boston, Massachusetts, to Jingzhou, China). Its simplicity and practicality have been recognized by both parties, and there were no technically related complications recorded. CONCLUSIONS: The MIMIT system allows for real-time, long-distance telecollaborative neuroendoscopic procedures and surgical training through a commercially available and inexpensive system. It enables remote experts to implement real-time, long-distance intraoperative interaction to guide inexperienced local surgeons, thus integrating the best medical resources and possibly promoting both diagnosis and treatment. Moreover, it can popularize and improve neurosurgical endoscopy technology in more hospitals to benefit more patients, as well as more neurosurgeons.