The joint impact of PM2.5 constituents on the risk of cerebrovascular diseases hospitalization: A large community-based cohort study.

Air pollution poses significant health risks to urban areas, with limited focus on the chronic association of PM2.5 and its constituents on cerebrovascular diseases (CERs), especially regarding the joint associations. This study explores the individual and joint associations between PM2.5 constituents and CER hospitalization risks through a cohort analysis of 36,271 adults in the Pearl River Delta, South China, from 2015 to 2020. Cox proportional hazards regression and quantile-based g-computation models were used to quantify the individual and joint associations of annual mean concentrations of PM2.5 constituents with hospitalization for CERs. 1151 participants were hospitalized due to CERs during the five-year follow-up period. Joint associations analyses identified that one quartile increase in co-exposure may result in hazard ratios of 1.530 (1.441-1.623), 1.840 (1.710-1.980), and 1.609 (1.491-1.737) for CERs, total, and ischemic stroke hospitalization, respectively. The adverse effect was primarily driven by organic matter and chlorine. Men, those with a history of tobacco or alcohol use or with low residential greenness, were more susceptible to CERs hospitalization following PM2.5 constituents co-exposure. Upcoming strategies should focus on monitoring and regulating PM2.5 constituents, encouraging healthy lifestyles, and enhancing urban greenery.

Glucose-induced RYBP suppresses tumor cell aerobic glycolysis and migration.

RYBP (Ring 1 and YY1 binding protein) has been frequently reported to play an important role during body development, stem cell differentiation, apoptosis and tumorigenesis, but whether RYBP carries out additional functions remains mysterious. Here, we demonstrated that RYBP protein levels elevate with increasing glucose concentration in cell culture medium in human tumorigenic cell lines, but an opposite trend was observed in non-tumorigenic cells. Mechanistic exploration disclosed that glucose inhibits polyubiquitination and proteasomal degradation, leading to RYBP stabilization in tumor cells. Further study showed that RYBP inhibits the glycolysis of tumor cells, as both extracellular acidification rate (ECAR) and lactate production increase when RYBP is knocked down, and decrease when RYBP is over-expressed, and this effect is unrelated to the glucose uptake ability of tumor cells. The functional study showed that RYBP is involved in the regulation of glucose on tumor cell migration. Compared to low glucose culture and their wildtypes, high glucose significantly enhanced tumor cell migration in RYBP knockdown or knockout tumor cells. Taken together, our current study uncovered a previously unknown function of RYBP in tumor metabolism, and this finding will enhance the exploration of the interplay between RYBP and nutrients during tumor cell metabolic reprogramming.

Global acetylome profiling indicates EPA impedes but OA promotes prostate cancer motility through altered acetylation of PFN1 and FLNA.

Prostate cancer (PCa) is one of the leading causes of cancer morbidity and mortality in men. Metastasis is the main cause of PCa-associated death. Recent evidence indicated a significant reduction in PCa mortality associated with higher ω-3 polyunsaturated fatty acids (PUFAs) consumption. However, the underlying mechanisms remained elusive. In this study, we applied global acetylome profiling to study the effect of fatty acids treatment. Results indicated that oleic acid (OA, monounsaturated fatty acid, MUFA, 100 µM) elevates while EPA (eicosapentaenoic acid, 100 µM) reduces the acetyl-CoA level, which alters the global acetylome. After treatment, two crucial cell motility regulators, PFN1 and FLNA, were found with altered acetylation levels. OA increased the acetylation of PFN1 and FLNA, whereas EPA decreased PFN1 acetylation level. Furthermore, OA promotes while EPA inhibits PCa migration and invasion. Immunofluorescence assay indicated that EPA impedes the formation of lamellipodia or filopodia through reduced localization of PFN1 and FLNA to the leading edge of cells. Therefore, perturbed acetylome may be one critical step in fatty acid-affected cancer cell motility. This study provides some new insights into the response of ω-3 PUFAs treatment and a better understanding of cancer cell migration and invasion modulation.

Hydrogen Ion Capturing Hydrogel Microspheres for Reversing Inflammaging.

Inflammaging is deeply involved in aging-related diseases and can be destructive during aging. The maintenance of pH balance in the extracellular microenvironment can alleviate inflammaging and repair aging-related tissue damage. In this study, the hydrogen ion capturing hydrogel microsphere (GMNP) composed of mineralized transforming growth factor-ß (TGF-ß) and catalase (CAT) nanoparticles is developed via biomimetic mineralization and microfluidic technology for blocking the NLRP3 cascade axis in inflammaging. This GMNP can neutralize the acidic microenvironment by capturing excess hydrogen ions through the calcium carbonate mineralization layer. Then, the subsequent release of encapsulated TGF-ß and CAT can eliminate both endogenous and exogenous stimulus of NLRP3, thus suppressing the excessive activation of inflammaging. In vitro, GMNP can suppress the excessive activation of the TXNIP/NLRP3/IL-1ß cascade axis and enhance extracellular matrix (ECM) synthesis in nucleus pulposus cells. In vivo, GMNP becomes a sustainable and stable niche with microspheres as the core to inhibit inflammaging and promote the regeneration of degenerated intervertebral discs. Therefore, this hydrogen ion-capturing hydrogel microsphere effectively reverses inflammaging by interfering with the excessive activation of NLRP3 in the degenerated tissues.

Learning curve of junior surgeons in robot-assisted pedicle screw placement: a comparative cohort study.

OBJECTIVE: Robot-assisted technology has been gradually applied to pedicle screw placement in spinal surgery. This study was designed to detailedly evaluate the learning curve of junior surgeons in robot-assisted spine surgery. METHODS: From December 2020 to February 2022, 199 patients requiring surgical treatment with posterior pedicle screw fixation were prospectively recruited into the study. The patients were randomized to the robot-assisted group (the RA group) or the conventional freehand group (the CF group). Under the senior specialist's supervision, pedicle screws were placed by two junior fellows without prior experience. Cumulative summation (CUSUM) analysis was performed on the learning curve of pedicle screw placement for performing quantitative assessment based on the time of screw insertion. RESULTS: In total, 769 and 788 pedicle screws were placed in the RA and CF groups. Compared with the CF group, the learning duration in the RA group was shorter in the upper thoracic region (57 vs. 70 screws), but longer in the lower thoracic (62 vs. 58 screws) and the lumbosacral region (56 vs. 48 screws). The slope of learning curve was lower in the RA group than in the CF group. The screw accuracy in the RA group was superior to that in the CF group, especially in upper thoracic region (89.4% vs. 76.7%, P < 0.001). This disparity of accuracy became wider in deformity cases. In the upper thoracic region, the mean placement time was 5.34 ± 1.96 min in the RA group and 5.52 ± 2.43 min in the CF groups, while in the lower thoracic and lumbosacral regions, the CF group's mean placement times were statistically shorter. Three screw-related neural complications occurred in the CF group. CONCLUSION: Robot-assisted technique has its advantages in the upper thoracic region and deformity cases, which is easier and safer to insert pedicle screws. The robot-assisted technique allowed a short learning curve for junior surgeons and exhibited consistently excellent results even in the early application period.

Comprehensive analysis of the lysine succinylome in fish oil-treated prostate cancer cells.

Prostate cancer (PCa) poses a significant health threat to males, and research has shown that fish oil (FO) can impede PCa progression by activating multiple mitochondria-related pathways. Our research is focused on investigating the impact of FO on succinylation, a posttranslational modification that is closely associated with mitochondria in PCa cells. This study employed a mass spectrometry-based approach to investigate succinylation in PCa cells. Bioinformatics analysis of these succinylated proteins identified glutamic-oxaloacetic transaminase 2 (GOT2) protein as a key player in PCa cell proliferation. Immunoprecipitation and RNA interference technologies validated the functional data. Further analyses revealed the significance of GOT2 protein in regulating nucleotide synthesis by providing aspartate, which is critical for the survival and proliferation of PCa cells. Our findings suggest that FO-dependent GOT2 succinylation status has the potential to inhibit building block generation. This study lays a solid foundation for future research into the role of succinylation in various biological processes. This study highlights the potential use of FO as a nutrition supplement for managing and slowing down PCa progression.

Hybrid fixation versus conventional cage-plate construct in 3-level ACDF: Introduce the "seesaw theory" of stand-alone cage.

STUDY DESIGN: A retrospective study. BACKGROUND: Conventional cage-plate construct (CCP) was widely used in anterior cervical discectomy and fusion (ACDF), but the rigid fixation limits the motion of fused segments. Self-locking stand-alone cage (SSC) was an alternative for ACDF procedures and showed several superiorities. However, the effect of hybrid fixation in 3-level ACDF remains unknown. OBJECTIVE: To assess the clinical and radiological outcomes of hybrid fixation with SSC and CCP against conventional CCP in 3-level ACDF. METHOD: A retrospective review of patients who underwent 3-level ACDF at Renji Hospital between January 2018 and December 2019 was performed. Eighty-three patients met the inclusion and exclusion criteria and were stratified into 2 groups based on the fixation methods. The clinical outcomes, functional outcomes, and radiological parameters were collected and analyzed. RESULTS: No significant difference was observed between the two groups in the mean age, sex, body mass index, hospital stay, and duration of follow-up. The postoperative C2-7 Cobb angle in the CCP group was significantly greater than that in the hybrid group. The rate of cervical proximal junctional kyphosis (CPJK) in the hybrid group was significantly lower than that in the CCP group. The CCP group suffered significantly higher rates of adjacent segment degeneration (ASD) than the hybrid group at 2 years postoperatively. Moreover, the incidence of postoperative dysphagia was lower in the hybrid group. No significant differences were observed in JOA and NDI scores between the two groups. CONCLUSION: The hybrid fixation achieved comparable clinical outcomes against CCP fixation, indicating that hybrid fixation is an alternative procedure in 3-level ACDF.

An atlas of anatomical variants of subsegmental pulmonary arteries and recognition error analysis.

Background: Surgery, including lobectomy and segmentectomy, is the major curative intervention for lung cancer. Surgical planning for pulmonary surgery is difficult due to the high variation rate of pulmonary arteries and needs a fine-grained atlas as a reference. We conducted a study to create a surgically oriented atlas and analyzed the error encountered during the production. Method: A total of 100 Chest CTs performed at Peking University People's Hospital from 2013.09 to 2020.10 were randomly selected for segmental artery labeling. Dicom files were collected for 3D reconstruction. Manual segmentation of each segmental artery was performed by 4 thoracic surgeons. Cross-validation by surgeons was performed to establish the golden standard based on their consensus. Initial recognition errors were recorded accordingly. Result: The most frequently seen variants for the right upper lobe is 2-branch RA1+2rec+3 and RA2asc; right middle lobe 2-branch RA4a and RA4b+5; right lower lobe 3-branch RA7, RA8 and RA9+10; left upper lobe 3-branch LA1+2a+3, LA1+2b, LA1+2c and 1-branch LA4+5; left lower lobe 2-branch LA8 and LA9+10. Top 5 segmental error occurs in RA4 (23%), LA8 (17%), RA9 (17%), RA8 (14%) and LA9 (11%). A rapid surgical planning tool form was created based on high frequency anatomic variants. Conclusion: Our research provided an atlas for lobectomy and segmentectomy at the subsegmental or more distal level. We demonstrated that the recognition accuracy of pulmonary arteries in a non-time-sensitive experimental scenario was still unfavorable. We also suggest that extra attention should be paid to certain surgeries during the surgical planning process.

Potential causal links between long-term ambient particulate matter exposure and cardiovascular mortality: New evidence from a large community-based cohort in South China.

BACKGROUND: Cardiovascular disease (CVD) mortality is associated with long-term particulate matter (PM) exposure. However, evidence from large, highly-exposed population cohort and observational-data-based causal inference approaches remains limited. AIMS: We examined the potential causal links between PM exposure and the CVD mortality in South China. METHODS: 580,757 participants were recruited during 2009-2015 and followed up through 2020. Satellite-based annual concentrations of PM2.5, PM10, and PMcoarse (i.e., PM10 - PM2.5) at 1 km2 spatial resolution were estimated and assigned to each participant. Marginal structural Cox models with time-varying covariates, adjusted using inverse probability weighting, were developed to evaluate the association between prolonged PM exposure and CVD mortality. RESULTS: For overall CVD mortality, the hazard ratios and 95% confidence interval for each 1 µg/m3 increase in the annual average concentration of PM2.5, PM10, and PMcoarse were 1.033 (1.028-1.037), 1.028 (1.024-1.032), and 1.022 (1.012-1.033), respectively. All three PMs were linked to a higher mortality risk for myocardial infarction and ischemic heart disease (IHD). The mortality risk of chronic IHD and hypertension was linked to PM2.5 and PM10. Significant association between PMcoarse and other heart disease mortality was also observed. The older, women, less-educated participants, or inactive participants exhibited particularly higher susceptibility. Participants who were generally exposed to PM10 concentrations below 70 µg/m3 were more vulnerable to PM2.5-, PM10- and PMcoarse-CVD mortality risks. CONCLUSION: This large cohort study provides evidence for the potential causal links between increased CVD mortality and ambient PM exposure, as well as socio-demographics linked to the highest vulnerability.

CircSMARCA5 silencing impairs cell proliferation and invasion via the miR-17-3p-EGFR signaling in lung adenocarcinoma.

AIMS: Circular RNAs are widely expressed in various cancers and play important roles in tumorigenesis and tumor progression. The function and mechanism of circSMARCA5 in lung adenocarcinoma however remains unclear. MAIN METHODS: QRT-PCR analysis was applied for determining circSMARCA5 expression in lung adenocarcinoma patient tumor tissues and cells. Molecular biological assays were used for investigating the role of circSMARCA5 in lung adenocarcinoma progression. Luciferase reporter and bioinformatics assays were used for identifying the underlying mechanism. KEY FINDINGS: In this study, we observed that circSMARCA5 expression was decreased in lung adenocarcinoma tissues but silencing of circSMARCA5 in lung adenocarcinoma cells inhibited cell proliferation, colony formation, migration and invasion. Mechanistically, we found EGFR, c-MYC and p21 were down-regulated upon circSMARCA5 knockdown. MiR-17-3p efficiently down- regulated EGFR expression via directly binding to EGFR mRNA. SIGNIFICANCE: These studies suggest that circSMARCA5 functions as an oncogene via targeting miR-17-3p-EGFR axis and may represent a promising therapeutic target for lung adenocarcinoma.

Circular RNA, circular RARS, promotes aerobic glycolysis of non-small-cell lung cancer by binding with LDHA.

PURPOSE: Accumulating evidence has highlighted the critical roles of circular RNAs (circRNAs) in non-small-cell lung cancer (NSCLC). This study aims to unveil the roles of circRARS (circular RARS) (hsa_circ_0001551) in NSCLC. METHODS: Quantitative real-time PCR was used to determine the expression of circRARS in NSCLC tissues and cells. Kaplan-Meier analysis was used to determine the prognostic value of circRARS expression. CCK8, transwell, and wound healing assays were used to assess the proliferation, invasion, and migration abilities of NSCLC cells. RNA pull-down, cell fraction, glucose consumption, lactate production, and lactate dehydrogenase activity assays were conducted to explore the potential mechanisms of circRARS in NSCLC. RESULTS: circRARS is upregulated in NSCLC tissues and positively correlated with smoking status, lymph node metastasis, and higher tumor stages. NSCLC patients with high expression of circRARS have poor overall survival. Functional assays demonstrated that circRARS accelerated the proliferation, invasion, and migration of NSCLC cells in vitro. The cell fraction suggested that circRARS mainly accumulated in cytoplasm and the RNA pull-down assay showed lactate dehydrogenase (LDHA) could bind with circRARS. Furthermore, circRARS positively regulates LDHA activity and LDHA expression at the transcription level. Moreover, downregulated circRARS decreases glucose consumption and lactate production and compromises aerobic glycolysis in NSCLC cells. Finally, rescue assays showed circRARS could promote NSCLC cell proliferation by regulating LDHA activity. CONCLUSION: This study shows that circRARS can promote glycolysis and tumor progression in NSCLC by regulating LDHA.

AI-based chest CT semantic segmentation algorithm enables semi-automated lung cancer surgery planning by recognizing anatomical variants of pulmonary vessels.

Background: The recognition of anatomical variants is essential in preoperative planning for lung cancer surgery. Although three-dimensional (3-D) reconstruction provided an intuitive demonstration of the anatomical structure, the recognition process remains fully manual. To render a semiautomated approach for surgery planning, we developed an artificial intelligence (AI)-based chest CT semantic segmentation algorithm that recognizes pulmonary vessels on lobular or segmental levels. Hereby, we present a retrospective validation of the algorithm comparing surgeons' performance. Methods: The semantic segmentation algorithm to be validated was trained on non-contrast CT scans from a single center. A retrospective pilot study was performed. An independent validation dataset was constituted by an arbitrary selection from patients who underwent lobectomy or segmentectomy in three institutions during Apr. 2020 to Jun. 2021. The golden standard of anatomical variants of each enrolled case was obtained via expert surgeons' judgments based on chest CT, 3-D reconstruction, and surgical observation. The performance of the algorithm is compared against the performance of two junior thoracic surgery attendings based on chest CT. Results: A total of 27 cases were included in this study. The overall case-wise accuracy of the AI model was 82.8% in pulmonary vessels compared to 78.8% and 77.0% for the two surgeons, respectively. Segmental artery accuracy was 79.7%, 73.6%, and 72.7%; lobular vein accuracy was 96.3%, 96.3%, and 92.6% by the AI model and two surgeons, respectively. No statistical significance was found. In subgroup analysis, the anatomic structure-wise analysis of the AI algorithm showed a significant difference in accuracies between different lobes (p = 0.012). Higher AI accuracy in the right-upper lobe (RUL) and left-lower lobe (LLL) arteries was shown. A trend of better performance in non-contrast CT was also detected. Most recognition errors by the algorithm were the misclassification of LA1+2 and LA3. Radiological parameters did not exhibit a significant impact on the performance of both AI and surgeons. Conclusion: The semantic segmentation algorithm achieves the recognition of the segmental pulmonary artery and the lobular pulmonary vein. The performance of the model approximates that of junior thoracic surgery attendings. Our work provides a novel semiautomated surgery planning approach that is potentially beneficial to lung cancer patients.

Minimally Invasive Full-endoscopic Posterior Cervical Foraminotomy and Discectomy: Introducing a Simple and Useful Localization Technique of the "V" Point.

OBJECTIVE: Conventional localization technique of V point for full-endoscopic posterior cervical foraminotomy and discectomy (FPCD) required repeated fluoroscopies, especially in patients with short and thick necks. To address this issue, the present study aimed to introduce a new localization technique of V point, and further evaluate its efficacy. METHODS: A K-wire was inserted and fixed at the pedicle eye under A/P fluoroscopy, then a working channel was established quickly along with it. Thirty-four patients who underwent minimally invasive FPCD assisted by the new technique were included in this study. The clinical and radiological data were collected and analyzed, including radiation dose, operative time, positioning time, visual analog scale (VAS) for neck and arm pain, neck disability index (NDI) scores, Cobb angle of operative level and range of motion of the cervical spine. RESULTS: All operations were performed successfully, and no iatrogenic nerve or vascular injury occurred. None of the patients needed to be transferred to open surgery or revision surgery. The mean radiation dose was found to be1.68 ± 0.36 mSv. The mean positioning time observed was 10.68 ± 5.42 min and the average operation time was 81.18 ± 10.87 min. The operation time significantly declined as the number of patients increased. A significant difference in operation time between the first (96.22 ± 10.36 min) and last quartile (75.00 ± 3.84 min) of cases was observed (t = 4.82, P < 0.001). The VAS scores for neck and arm pain, and NDI scores were significantly improved after surgery (PVAS-Neck <0.0001, PVAS-Arm <0.0001, PNDI <0.0001). Based on MacNab criteria, the excellent plus good rate was 91.17%. The Cobb angle of operative level and range of motion of the cervical spine were significantly improved postoperatively (t = 2.846, POA  = 0.015; t = 2.232, PROM-CA  = 0.026). CONCLUSION: The new image-assisted V point localization technique is simple and useful with little radiation exposure and short positioning time. FPCD assisted by the new technique could be a safe and effective alternative on properly selected patients.

C-type lectin domain-containing protein CLEC3A regulates proliferation, regeneration and maintenance of nucleus pulposus cells.

It is widely assumed that as connective tissue, the intervertebral disc (IVD) plays a crucial role in providing flexibility for the spinal column. The disc is comprised of three distinct tissues: the nucleus pulposus (NP), ligamentous annulus fibrous (AF) that surrounds the NP, and the hyaline cartilaginous endplates (CEP). Nucleus pulposus, composed of chondrocyte-like NP cells and its secreted gelatinous matrix, is critical for disc health and function. The NP matrix underwent dehydration accompanied by increasing fibrosis with age. The degeneration of matrix is almost impossible to repair, with the consequence of matrix stiffness and senescence of NP cells and intervertebral disc, suggesting the value of glycoproteins in extracellular matrix (ECM). Here, via database excavation and biological function screening, we investigated a C-type lectin protein, CLEC3A, which could support differentiation of chondrocytes as well as maintenance of NP cells and was essential to intervertebral disc homeostasis. Furthermore, mechanistic analysis revealed that CLEC3A could stimulate PI3K-AKT pathway to accelerate cell proliferation to further play part in NP cell regeneration.

Total nodule number as an independent prognostic factor in resected stage III non-small cell lung cancer: a deep learning-powered study.

Background: Almost every patient with lung cancer has multiple pulmonary nodules; however, the significance of nodule multiplicity in locally advanced non-small cell lung cancer (NSCLC) remains unclear. Methods: We identified patients who had undergone surgical resection for stage I-III NSCLC at the Peking University People's Hospital from 2005 to 2018 for whom preoperative chest computed tomography (CT) scans were available. Deep learning-based artificial intelligence (AI) algorithms using convolutional neural networks (CNN) were applied to detect and classify pulmonary nodules (PNs). Maximally selected log-rank statistics were used to determine the optimal cutoff value of the total nodule number (TNN) for predicting survival. Results: A total of 33,410 PNs were detected by AI among the 2,126 participants. The median TNN detected per person was 12 [interquartile range (IQR) 7-20]. It was revealed that AI-detected TNN (analyzed as a continuous variable) was an independent prognostic factor for both recurrence-free survival (RFS) [hazard ratio (HR) 1.012, 95% confidence interval (CI): 1.002 to 1.022, P=0.021] and overall survival (OS) (HR 1.013, 95% CI: 1.002 to 1.025, P=0.021) in multivariate analyses of the stage III cohort. In contrast, AI-detected TNN was not significantly associated with survival in the stage I and II cohorts. In a survival tree analysis, rather than using traditional IIIA and IIIB classifications, the model grouped cases according to AI-detected TNN (lower vs. higher: log-rank P<0.001), which led to a more effective determination of survival rates in the stage III cohort. Conclusions: The AI-detected TNN is significantly associated with survival rates in patients with surgically resected stage III NSCLC. A lower TNN detected on preoperative CT scans indicates a better prognosis for patients who have undergone complete surgical resection.

A fully automated noncontrast CT 3-D reconstruction algorithm enabled accurate anatomical demonstration for lung segmentectomy.

BACKGROUND: Three-dimensional reconstruction of chest computerized tomography (CT) excels in intuitively demonstrating anatomical patterns for pulmonary segmentectomy. However, current methods are labor-intensive and rely on contrast CT. We hereby present a novel fully automated reconstruction algorithm based on noncontrast CT and assess its performance both independently and in combination with surgeons. METHODS: A retrospective pilot study was performed. Patients between May 2020 to August 2020 who underwent segmentectomy in our single institution were enrolled. Noncontrast CTs were used for reconstruction. In the first part of the study, the accuracy of the demonstration of anatomical variants by either automated or manual reconstruction algorithm were compared to surgical observation, respectively. In the second part of the study, we tested the accuracy of the identification of anatomical variants by four independent attendees who reviewed 3-D reconstruction in combination with CT scans. RESULTS: A total of 20 cases were enrolled in this study. All segments were represented in this study with two left S1-3, two left S4 + 5, one left S6, five left basal segmentectomies, one right S1, three right S2, 1 right S2b + 3a, one right S3, two right S6 and two right basal segmentectomies. The median time consumption for the automated reconstruction was 280 (205-324) s. Accurate vessel and bronchial detection were achieved in 85% by the AI approach and 80% by Mimics, p = 1.00. The accuracy of vessel classification was 80 and 95% by AI and manual approaches, respectively, p = 0.34. In real-world application, the accuracy of the identification of anatomical variant by thoracic surgeons was 85% by AI+CT, and the median time consumption was 2 (1-3) min. CONCLUSIONS: The AI reconstruction algorithm overcame defects of traditional methods and is valuable in surgical planning for segmentectomy. With the AI reconstruction, surgeons may achieve high identification accuracy of anatomical patterns in a short time frame.

Baseline and Process Factors of Anti-Retroviral Therapy That Predict Loss to Follow-up Among People Living with HIV/AIDS in China: A Retrospective Cohort Study.

We explored the predictors and predictive models of loss to follow-up (LTFU) during the first year of anti-retroviral therapy (ART). LTFU was defined as the failure to visit the clinic for antiretroviral drugs for ≥ 90 days after the last missed scheduled visit. Based on the electronic medical records of 5953 patients who were HIV positive and began ART between 2016 and 2019 in China, the LTFU rate was 7.24 (95% confidence interval 6.49-7.97) per 100 person-years during the first year of ART. ART baseline factors were associated with LTFU, but were non-optimal predictors. A model including ART process-related factors such as follow-up behaviors and physical health status had an area under the receiver operating characteristic curve of 73.4% for predicting LTFU. Therefore, the medical records of follow-up visits can be used to identify patients with a high risk of LTFU and allow interventions to be implemented proactively.

Electrospun Fibers Improving Cellular Respiration via Mitochondrial Protection.

Cellular respiration is the prerequisite for cell survival and functions, and mitochondrial function and microcirculation oxygen supply are essential for cellular respiration. However, in diabetic fracture, cellular respiration of bone marrow stem cells (BMSCs) is disrupted because of the dysfunction of mitochondria and microcirculation disorders. Here, the electrospun fibers of GelMA loaded with Hif-1 pathway activator (DFO) are constructed to improve the cellular respiration of BMSCs via protecting mitochondrial function and reconstructing microcirculation. The sequential process of electrospinning and UV crosslinking endowed the electrospun fibers with breathability and the biomechanical properties like the periosteum. In vitro biomolecular experiments showed that by crosslinking grafted polyethylene glycol acrylate liposomes loaded with DFO, the functional electrospun fibers can release DFO locally to activate Hif-1 in BMSCs, which can regulate the balance of Bcl-2/Bax to protect mitochondria and upregulate the expression of VEGF to reconstruct microcirculation. Animal experiments confirmed that the functional electrospun fibers can promote the recovery of diabetic fracture in vivo. These suggested that the functional electrospun fibers can improve cellular respiration for cell survival and functions of BMSCs. This study provides a new treatment strategy for diabetic fracture and other tissue regeneration on basis of cellular respiration improvement.

Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week.

While the potential of patient-derived organoids (PDOs) to predict patients' responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings.

Mental Health Help-Seeking and Associated Factors Among Public Health Workers During the COVID-19 Outbreak in China.

Background: The COVID-19 outbreak in China has created multiple stressors that threaten individuals' mental health, especially among public health workers (PHW) who are devoted to COVID-19 control and prevention work. This study aimed to investigate the prevalence of mental help-seeking and associated factors among PHW using Andersen's Behavioral Model of Health Services Use (BMHSU). Methods: A cross-sectional survey was conducted among 9,475 PHW in five provinces across China between February 18 and March 1, 2020. The subsample data of those who reported probable mental health problems were analyzed for this report (n = 3,417). Logistic and hierarchical regression analyses were conducted to examine the associations of predisposing, enabling, need, and COVID-19 contextual factors with mental health help-seeking. Results: Only 12.7% of PHW reported professional mental help-seeking during the COVID-19 outbreak. PHW who were older, had more days of overnight work, received psychological training, perceived a higher level of support from the society, had depression and anxiety were more likely to report mental help-seeking (ORm range: 1.02-1.73, all p < 0.05) while those worked in Centers for Disease Control and Prevention were less likely to seek help (ORm = 0.57, p < 0.01). The belief that mental health issues were not the priority (64.4%), lack of time (56.4%), and shortage of psychologists (32.7%) were the most frequently endorsed reasons for not seeking help. Conclusions: The application of BMHSU confirmed associations between some factors and PHW's mental health help-seeking. Effective interventions are warranted to promote mental health help-seeking of PHW to ameliorate the negative impact of mental illness and facilitate personal recovery and routine work.