An Atmospheric Water-Harvester with Ultrahigh Uptake-Release Efficiency at Low Humidity.

Atmospheric water harvesting is a practical strategy that is achieved by removing materials from air moisture to relieve global water scarcity. Here we design a water-harvester (i.e., MOF-303/thiolated polymer composite (MTC)) by using a metal-organic framework (MOF-303) and thiolated chitosan (TC) skeleton. Intermolecular hydrogen bonding between TC and MOF-303 facilitates porous structures with enlarged air-polymer interfaces for long cycling life and high capacity at low relative humidity. Benefiting from synergetic effects on porosity and anchorage for accelerating the uptake-release of moisture, MTC exhibits a rapid water uptake capacity of 0.135 g/g in 60 min under 12.5 RH% and ultrafast water desorption kinetics of 0.003 g/g/min at 8.5 RH%, which is superior to the as-reported MOF-303 based adsorbents. At low heat (∼40 °C), the water desorption and collection rate, respectively, are 0.0195 and 0.0168 g/g/min within 210 min, showing ultrahigh harvesting efficiency. These results highlight the enormous potential as promising materials for solving the world's water scarcity crisis. This study offers an insight into the design of AWH materials, which can be extended into applications in some realms, e.g., freshwater development for industry in arid areas, water engineering-related devices and systems, etc.

Gradient-Janus Wires for Simultaneous Fogwater Harvesting and Electricity Generation.

A Gradient-Janus wire (GJW) with a diameter of 0.3 mm has been fabricated on a large scale through liquid confined modification, enabling the opposite conical wetting phenomenon along the same orientation of the GJW, characterized by an increasing superhydrophilic region and a decreasing hydrophobic region. This property allows the GJW to exhibit controllable water hovering, transport, and pinning during fog harvesting, i.e., at a large tilting angle α of 60° (mass increased with decreased α), the GJW can hover 0.6 mg of harvested fogwater in 30 s, can transport 3 mg of fogwater along the gradient in 30 s at α = 4° (with maximal mass reaching up to 4.3 mg at α = -10°), and finally, pin the water droplet at the end of the GJW. Such ability generates an effective torque that serves as the driving force for rotation. We designed a GJWs-wheel by radially arranging 60 GJWs together, resulting in an extremely lightweight structure weighing only 1.9 g. The cumulative torque generated during fog harvesting activates the rotation of the GJWs-wheel. When loaded with a coil within a magnetic field, electricity is generated as output power peaks at around 0.25 µW while maintaining a high water harvesting efficiency averaging approximately 38 ± 2.12 mg/min. This finding is significant as it provides valuable insights into designing materials capable of efficiently harnessing both energy and water resources.

High-speed imaging of supersaturated cavitation clouds and the vibration modes of the radiation surface of high-power transducers.

The vibration mode of the radiation surface of transducer (or structure of supersaturated cavitation cloud in thin liquid) is investigated experimentally by high-speed photography. The classification of saturated, supersaturated and undersaturated cavitation clouds was proposed, and a comparison was made between saturated and supersaturated cavitation cloud structures in liquid thin layers. The characteristics and formation mechanism of supersaturated cavitation cloud structure were investigated. Based on the close correspondence and rapid response between the distribution of supersaturated cavitation clouds and vibration modes of radiation surface, a new approach is proposed to measure the vibration mode of transducer operating at high power and large amplitude in real time.

Collapsing behavior of spark-induced cavitation bubble in rigid tube.

The phenomenon of cavitation within tubes is a common scenario in the fields of medicine and industry. This paper focuses on the effects of rigid circular tube length, diameter and the distance of bubble - tube port on the behavior of bubble in tube. The low-voltage discharge technique was utilized to induce a cavitation bubble in deionized water. The effects of rigid tube lengths, diameters, and bubble-tube port distances on the morphology of bubbles are observed using high-speed camera. It has been found that as the length of the rigid tube increases, so does the period, and this effect is more pronounced in tubes with smaller diameters. Conversely, the cavitation bubble period decreased and then stabilized as the tube diameter increased, the ratio of tube radius and the bubble radius exceeds 4.8, the period of bubble in tube is similar to that of bubble in free field. Further analysis of the influence of tube characteristics on microjets reveals that a pair of oppositely microjets were formed along the tube axis by the bubble near the midpoint of the tube axis. Moreover, when the non-dimensional tube length η < 3.5, the increase tube diameter results in a decrease microjet velocity. It has also been observed that as the bubble gradually approaches the interior of the tube, the velocity of microjets directed inward decreases. Additionally, the smaller the diameter of the tube, the greater the bubble-tube port distance required for the microjets to reach the same level of velocity as bubble near the center of the tube axis. These findings hold theoretical implications for improvement of targeted drug delivery efficiency in medicine and enhance the operational efficiency of inertial micropumps in industries.

Robust Photothermal Icephobic Surface with Mechanical Durability of Multi-Bioinspired Structures.

Photothermal superhydrophobic surfaces are potential to become ideal anti-/deicing surfaces due to their rapid water removal, icing delay, and photothermal deicing performance. Here, a robust photothermal icephobic surface with mechanical durability is shown that is integrated with a microspine array inspired by honeycomb and cactus thorn (i.e., MAHC), which is developed by a laser-layered microfabrication strategy. The maximum stress on the microspine of the MAHC is reduced by ≈2/3, due to the protection of the bionic honeycomb structure. Even after 200 linear abrasions by a steel blade, the MAHC remains superior water repellency with a water contact angle of 150.7° and roll-off angles of 10.3°, stable icing delay time (578.2 s), and rapidly photothermal deicing capabilities (401 s). As the MAHC is fabricated on a curvature surface such as a copper alloy transmission line for an overhead high-speed rail, a stable photothermal anti-/deicing in a low-temperature environment still can be achieved effectively. The freezing rain covering the functional transmission line completely slides off within 758 s under one sun illumination. This studying offers insight into the design of novel materials with stable anti-icing/icephobic structures, which would be extended into some applied realms, for example, transportation fields or power systems in cold or low-temperature climates.

MicroRNA PC-5p-3991_515 mediates triflumezopyrim susceptibility in the small brown planthopper through regulating the post-transcriptional expression of P450 CYP417A2.

BACKGROUND: Cytochrome P450 monooxygenases (P450s) are recognized as a major contributor to metabolic resistance in insects to most insecticides, through gene overexpressions and protein mutations. MicroRNA (miRNA), an important post-transcriptional regulator, has been reported to promote insecticide resistance by mediating the expression of detoxification enzyme genes. RESULTS: In the present study, we reported that a novel microRNA PC-5p-3991_515 was involved in the post-transcriptional regulation of CYP417A2 and mediated the triflumezopyrim susceptibility in the small brown planthopper (SBPH), Laodelphax striatellus (Fallén). The tissue expression profiles showed that CYP417A2 was highly expressed in fat body. CYP417A2 was significantly up-regulated at 12, 36, 60, 84 and 108 h after the triflumezopyrim treatment. RNA interference (RNAi) against CYP417A2 significantly increased triflumezopyrim susceptibility in SBPH. According to the prediction by miRanda and TargetScan software, three miRNAs were indicated to bind to CYP417A2. However, when oversupply of agomir, only two miRNAs, PC-3p-625_4405 and PC-5p-3991_515, significantly increased the susceptibility to triflumezopyrim and decreased CYP417A2 levels. Furthermore, PC-5p-3991_515 was confirmed to be involved in the post-transcriptional regulation of CYP417A2 by dual luciferase reporter assay. Meanwhile, PC-5p-3991_515 was co-localized with CYP417A2 in the midgut in situ hybridization. CONCLUSION: Our findings revealed that the novel microRNA, PC-5p-3991_515, post-transcriptionally regulated CYP417A2 expression, which then mediated the triflumezopyrim susceptibility in SBPH. © 2023 Society of Chemical Industry.

Novel spatial profiles of some diffusive SIS epidemic models.

In this paper, we are concerned with two SIS epidemic reaction-diffusion models with mass action infection mechanism of the form SI, and study the spatial profile of population distribution as the movement rate of the infected individuals is restricted to be small. For the model with a constant total population number, our results show that the susceptible population always converges to a positive constant which is indeed the minimum of the associated risk function, and the infected population either concentrates at the isolated highest-risk points or aggregates only on the highest-risk intervals once the highest-risk locations contain at least one interval. In sharp contrast, for the model with a varying total population number which is caused by the recruitment of the susceptible individuals and death of the infected individuals, our results reveal that the susceptible population converges to a positive function which is non-constant unless the associated risk function is constant, and the infected population may concentrate only at some isolated highest-risk points, or aggregate at least in a neighborhood of the highest-risk locations or occupy the whole habitat, depending on the behavior of the associated risk function and even its smoothness at the highest-risk locations. Numerical simulations are performed to support and complement our theoretical findings.

Hepatorenal pathologies in TNF-transgenic mouse model of rheumatoid arthritis are alleviated by anti-TNF treatment.

OBJECTIVE: To examine and quantify liver and kidney lesions and their response to anti-tumor necrosis factor (TNF) therapy in a TNF-Tg mouse model of rheumatoid arthritis (RA). METHODS: Female TNF-Tg (Tg3647) mice were used as the animal model for chronic RA. Ultrasound, immunofluorescence, histological staining, serology tests, and real-time RT-PCR were used to examine the pathological changes in the liver and kidney. RESULTS: TNF-Tg mice showed a significant decrease in the body weight and a dramatic increase in the volumes of the gallbladder, knee cavity, and popliteal lymph nodes. The liver and kidneys of TNF-Tg mice showed increased chronic inflammation and accumulation of immune cells and fibrosis, compared to wild-type (WT) mice. Moreover, upregulation of inflammatory factors and impaired normal function were observed in the liver and kidneys of TNF-Tg mice. Inflammatory infiltration and fibrosis of the liver and kidneys of female TNF-Tg mice were improved after anti-TNF treatment, and better treatment effects were achieved at 4.5-month-old mice when they were received 8 weeks of intervention. CONCLUSIONS: We found that TNF drives the development of liver and kidney pathology in female TNF-Tg mice and that there are limitations to the loss of utility of anti-TNF for the prolonged treatment of RA-associated hepatic and renal injury. This study provides a reliable and clinically relevant animal model for further studies exploring the molecular mechanisms and drug discovery for hepatorenal pathologies in RA.

Highly Efficient Photothermal Icephobic/de-Icing MOF-Based Micro and Nanostructured Surface.

Photothermal materials have gained considerable attention in the field of anti-/de-icing due to its environmental friendliness and energy saving. However, it is always significantly challenging to obtain solar thermal materials with hierarchical structure and simultaneously demonstrate both the ultra-long icing delay ability and the superior photothermal de-icing ability. Here, a photothermal icephobic MOF-based micro and nanostructure surface (MOF-MNS) is presented, which consists of micron groove structure and fluorinated MOF nanowhiskers. The optimal MOF-M250 NS can achieve solar absorption of over 98% and produce a high temperature increment of 65.5 °C under 1-sun illumination. Such superior photothermal-conversion mechanism of MOF-M250 NS is elucidated in depth. In addition, the MOF-M250 NS generates an ultra-long icing delay time of ≈3960 s at -18 °C without solar illumination, achieving the longest delay time, which isn't reported before. Due to its excellent solar-to-heat conversation ability, accumulated ice and frost on MOF-M250 NS can be rapidly melted within 720 s under 1-sun illumination and it also holds a high de-icing rate of 5.8 kg m-2 h-1 . MOF-M250 NS possesses the versatility of mechanical robustness, chemical stability, and low temperature self-cleaning, which can synergistically reinforce the usage of icephobic surfaces in harsh conditions.

Effects of combining immune checkpoint inhibitors and anti-angiogenic agents on bone metastasis in non-small cell lung cancer patients.

This study aimed to evaluate the efficacy of combining immune checkpoint inhibitors (ICIs) and anti-angiogenic agents in treating lung cancer patients with bone metastases (BMs), as it is unclear whether this combination is effective for this condition. Non-small cell lung cancer patients with BMs receiving ICIs were divided into experimental and control groups based on anti-angiogenic treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, with log-rank test for comparisons. Prognostic factors were determined by univariate and multivariate Cox regression analyses. The study included 95 patients. The experimental group (n = 42) had a higher disease control rate (DCR) (90.5% vs. 68.6%, p = .009), objective response rate (ORR) (35.7% vs. 24.5%, p = .235), and longer median bone PFS (14.3 months vs. 8.3 months, p = .011) for bone metastasis. However, there were no significant differences in overall DCR (92.8% vs. 86.7%, p = .339), ORR (64.3% vs. 62.3%, p = .839), and PFS (12.4 months vs. 11.6 months, p = 0.383) between the 2 groups. The experimental group had a lower incidence of skeleton-related events (SREs) (28.6% vs. 35.8%, p = .425), and SRE patients had shorter PFS (7.7 vs. 14.3 months, p < .001) and OS (12.1 vs. 19.0 months, p = .028). Anti-angiogenic therapy (HR = 0.55, p = .012) and SRE (HR = 2.93, p < .001) were identified as independent prognostic factors for bone metastatic PFS. Adverse events were slightly higher in the experimental group (29.3% vs. 18.9%, p = .238), but not statistically significant. The combination of ICIs and anti-angiogenic agents leads to a significant PFS for BMs and potentially decreases SRE.

A retrospective real-world experience of immunotherapy in patients with extensive stage small-cell lung cancer.

BACKGROUND: The treatment of extensive stage small-cell lung cancer (ES-SCLC) has only made modest progress in the past decade, with two immune checkpoint inhibitors (ICIs), atezolizumab and durvalumab, approved for the treatment of SCLC by January 2022. However, currently, there is limited real-world data on ES-SCLC patients received immunotherapy. METHODS: We retrospectively collected and analyzed the demographic and treatment data of ES-SCLC patients at the First Affiliated Hospital of Guangzhou Medical University from January 2017 to January 2022. Survival and prognosis information was obtained through follow-up. RESULTS: A total of 353 ES-SCLC patients were included, of which 165 received immunotherapy combined with chemotherapy as the first-line (FL) treatment (chemo-immune group), and 188 received chemotherapy (chemotherapy group). The objective response rate (ORR) and disease control rate (DCR) of patients receiving immunotherapy as the FL treatment were better than the chemotherapy group (76.97% vs. 48.40%, p < 0.001, and 83.03% vs. 68.09%, p < 0.001). Moreover, the progression-free survival (PFS) and overall survival (OS) of ES-SCLC patients receiving immunotherapy as the FL treatment were better than the chemotherapy group (6.7 months vs. 5.1 months, p < 0.001, and 12.5 months vs. 11.2 months, p < 0.001). Furthermore, the OS of ES-SCLC patients who received immunotherapy as second-line treatment was better than that in the chemotherapy group (15.9 months vs. 12.9 months, p = 0.036). CONCLUSION: ICIs combined with chemotherapy as the FL treatment could be beneficial to the ORR, DCR, PFS, and OS of ES-SCLC patients. Furthermore, ES-SCLC patients can benefit from ICIs in the second-line treatment, even if they had not received ICIs in the FL treatment.

Efficient Atmospheric Water Harvesting of Superhydrophilic Photothermic Nanocapsule.

Drought and water scarcity are two of the world's major problems. Solar-powered sorption-based atmospheric water harvesting technology is a promising solution in this category. The main challenge is to design materials with high water harvesting performance while achieving fast water vapor adsorption/desorption rates. Here, a superhydrophilic photothermic hollow nanocapsule (SPHN) is represented that achieves efficient atmospheric water harvesting in outdoor climates. In SPHN, the hollow mesoporous silica (HMS) is grafted with polypyrrole (PPy) and also loaded with lithium chloride (LiCl). The hollow structure is used to store water while preventing leakage. The hydrophilic spherical nanocapsule and the trapped water produce more free and weakly adsorbed water. Significantly lower the heat of desorption compared to pure LiCl solution. Such SPHN significantly improves the adsorption/desorption kinetics, e.g., absorbs 0.78-2.01 g of water per gram of SPHN at 25 °C, relative humidity (RH) 30-80% within 3 h. In particular, SPHN has excellent photothermal properties to achieve rapid water release under natural sunlight conditions, i.e., 80-90% of water is released in 1 h at 0.7-1.0 kW m-2 solar irradiation, and 50% of water is released even at solar irradiation as low as 0.4 kW m-2 . The water collection capacity can reach 1.2 g g-1 per cycle by using the self-made atmospheric water harvesting (AWH) device. This finding provides a way to design novel materials for efficient water harvesting tasks, e.g., water engineering, freshwater generator, etc.

Comparing the Accuracy of Seven Scoring Systems in Predicting Survival of Lung Cancer Patients With Spinal Metastases: An External Validation From Two Centers.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To investigate the accuracy of seven scoring systems for the prediction of survival in lung cancer patients with spinal metastases (SPM). SUMMARY OF BACKGROUND DATA: Although survival scoring systems have been developed for surgical decision-making, the reliability and validity of these models are unclear for specific cancer types. As the prevalence of patients with lung cancer increases, it is imperative to determine the accuracy of these models for lung cancer patients with SPM. MATERIALS AND METHODS: This is a retrospective study of a cohort of lung cancer patients with SPM who underwent spine surgery between 2019 and 2021 at two centers. The optimal area under the curve (AUC) was calculated to evaluate the accuracy of seven candidate scoring systems at 3, 6, and 12 months. Calibration and decision curve analysis was used for further validation. RESULTS: A total of 166 patients (mean age: 58.98±10.94; 105 males and 61 females) with SPM were included. The median postoperative survival was 12.87±0.93 months. The modified Bauer score, revised Tokuhashi score, Linden score, Tomita score, the Skeletal Oncology Research Group nomogram, and the New England Spinal Metastasis Score in prediction survival at 3, 6, and 12 months showed a slightly weaker AUC (range 0.464-0.659). The AUC of the Katagiri-New score in predicting 1-year survival for lung cancer patients was the highest (0.708; range 0.619-0.798). The decision curve analysis showed that the Katagiri-New score led to a greater net benefit than the strategies of changing management for all patients or none of the patients. CONCLUSIONS: This study suggests that the most commonly used models have limitations in predicting survival in patients undergoing spinal surgery for metastatic lung cancer and underestimate survival. In this sample of lung cancer patients, the Katagiri-New Scoring system score had the best performance in predicting 1-year survival. LEVEL OF EVIDENCE: 4.

Genomic characterisation of de novo EGFR copy number gain and its impact on the efficacy of first-line EGFR-tyrosine kinase inhibitors for EGFR mutated non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation generally respond well to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). However, genomic characterisation of de novo EGFR copy number gain (CNG) and its impact on the efficacy of first-line EGFR-TKIs remains unclear. METHODS: This multicenter, retrospective and real-world study included two cohorts that enroled EGFR mutant NSCLC patients. EGFR CNG was tested by next-generation sequencing of untreated tissue specimens. Cohort 1 detected the impact of EGFR CNG on first-line EGFR-TKIs treatment, and cohort 2 explored the genomic characterisation. RESULTS: Cohort 1 enroled 355 patients from four cancer centres between January 2013 and March 2022. The patients were divided into three groups, included the EGFR non-CNG, EGFR CNG, and EGFR uncertain-CNG. No significant difference in progression-free survival (PFS) was found between the three groups (10.0 months vs. 10.8 months vs. 9.9 months, respectively, p = 0.384). Furthermore, the overall response rate was not statistically significant in the EGFR CNG group compared to the EGFR non-CNG or uncertain arm (70.3% vs. 63.2% vs. 54.5%, respectively, p = 0.154). Cohort 2 included 7876 NSCLC patients with 16.4% showing EGFR CNG. Gene mutations such as TP53, IKZF1, RAC1, MYC, MET, CDKN2A/B and alterations of the metabolic-related and ERK signalling pathway were significantly associated with patients with EGFR CNG compared to those without. CONCLUSIONS: De novo EGFR CNG had no effect on the efficacy of first-line EGFR-TKI treatment in EGFR mutant NSCLC patients, and tumours with EGFR CNG had more complex genomic profiles than those without.

Real-world data on severe lung cancer: a multicenter retrospective study.

Background: Severe lung cancer is a novel concept that describes a patient with poor performance status (PS; 2-4) but with a high probability of receiving survival benefit and improvement in the PS score. However, there is currently no relevant research or real-world data on those with severe lung cancer, such as incidence, cause, clinical features, and risk factors. Methods: The data from patients with advanced lung cancer attending multiple centers from January 1, 2022, to June 30, 2022, were collected for a cross-sectional study. In addition, data from fatal cases from January 1, 2019, to June 30, 2022, were retrospectively collected as another cohort. And we developed a questionnaire to assess clinicians' mastery of severe lung cancer. Results: Three participating institutes enrolled the data set of 1,725 patients, and the dataset of 269 fatal cases were included in another cohort; the incidence of severe lung cancer was 13.10% and 37.55%, respectively. Severe lung cancer patients were mainly stage IV elderly male patients without gene mutation and a history of resection. And the proportion of smoking and comorbidities in severe lung cancer patients is more than in non-severe lung cancer patients (50.4% vs. 40.8%, P=0.006; 46.9% vs. 36.4%, P=0.002). Treatment-related adverse events (AEs) (46.0%) accounted for the largest proportion of the primary causes of severe lung cancer in the cross-sectional study, while cancer-related symptoms (54.5%) accounted for the largest proportion of the primary causes of sever lung cancer in the 101 fatal cases. For the fatal cases, the overall survival of severe lung cancer patients caused by cancer-related symptoms was longer than that caused by treatment-related AEs (8 vs. 3 months; P=0.019). A total of 616 clinicians completed the questionnaire; 90.26% of clinicians agreed with the concept of severe lung cancer. Conclusions: The incidence of severe lung cancer cannot be ignored based on real-world data. Treatment-related AEs are gradually account for more of the causes of severe lung cancer, surpassing cancer-related symptoms and comorbidities. Furthermore, the prognosis of patients with advanced lung cancer who develop severe lung cancer due to treatment-related AEs is worse than cancer-related symptoms.

A Risk-Scoring Model for Severe Checkpoint Inhibitor-Related Pneumonitis: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Checkpoint inhibitor-related pneumonitis (CIP) is one of the most common serious and fatal adverse events associated with immune checkpoint inhibitors (ICIs). The study sought to identify risk factors of all-grade and severe CIP and to construct a risk-scoring model specifically for severe CIP. METHODS: This observational, retrospective case-control study involved 666 lung cancer patients who received ICIs between April 2018 and March 2021. The study analyzed patient demographic, preexisting lung diseases, and the characteristics and treatment of lung cancer to determine the risk factors for all-grade and severe CIP. A risk score for severe CIP was developed and validated in a separate patient cohort of 187 patients. RESULTS: Among 666 patients, 95 patients were afflicted with CIP, of which 37 were severe cases. Multivariate analysis revealed age ≥ 65 years, current smoking, chronic obstructive pulmonary disease, squamous cell carcinoma, prior thoracic radiotherapy, and extra-thoracic radiotherapy during ICI were independently associated with CIP events. Five factors, emphysema (odds ratio [OR] 2.87), interstitial lung disease (OR 4.76), pleural effusion (OR 3.00), history of radiotherapy during ICI (OR 4.30), and single-agent immunotherapy (OR 2.44) were independently associated with severe CIP and were incorporated into a risk-score model (score ranging 0-17). The area under the model receiver operating characteristic curve for the model was 0.769 in the development cohort and 0.749 in the validation cohort. CONCLUSIONS: The simple risk-scoring model may predict severe CIP in lung cancer patients receiving ICIs. For patients with high scores, clinicians should use ICIs with caution or strengthen the monitoring of these patients.

External validation of the SORG machine learning algorithms for predicting 90-day and 1-year survival of patients with lung cancer-derived spine metastases: a recent bi-center cohort from China.

BACKGROUND CONTEXT: The survival prediction of lung cancer-derived spinal metastases is often underestimated by several scores. The SORG machine learning (ML) algorithm is considered a promising tool to predict the risk of 90-day and 1-year mortality in patients with spinal metastases, but not been externally validated for lung cancer. PURPOSE: This study aimed to externally validate the SORG ML algorithms on lung cancer-derived spinal metastases patients from two large-volume, tertiary medical centers between 2018 and 2021. STUDY DESIGN/SETTING: Retrospective, cohort study. PATIENT SAMPLE: Patients aged 18 years or older at two tertiary medical centers in China are treated surgically for spinal metastasis. OUTCOME MEASURES: Mortality within 90 days of surgery, mortality within 1 year of surgery. METHODS: The baseline characteristics were compared between the development cohort and our validation cohort. Discrimination (receiver operating curve), calibration (calibration plot, intercept, and slope), the overall performance (Brier score), and decision curve analysis was used to assess the overall performance of the SORG ML algorithms. RESULTS: This study included 150 patients with lung cancer-derived spinal metastases from two medical centers in China. Ninety-day and 1-year mortality rates were 12.9% (19/147) and 51.3% (60/117), respectively. Lung Cancer with targeted therapies had the lowest Hazard Ratio (HR=0.490), showing an optimal protecting factor. The AUC of the SORG ML algorithm for 90-day mortality prediction in lung cancer-derived spinal metastases is 0.714. While the AUC for 1-year mortality prediction is 0.832 (95CI%, 0.758-0.906). The algorithm for 1-year mortality was well-calibrated with an intercept of 0.13 and a calibration slope of 1.00. However, the 90-day mortality prediction was underestimated with an intercept of 0.60 and a slope of 0.37. The SORG ML algorithms for 1-year mortality showed a greater net benefit than the "treats all or no patients" strategies. CONCLUSIONS: In the latest cohort of lung cancer-derived spinal metastases in China, the SORG algorithms for predicting 1-year mortality performed well on external validation. However, 90-day mortality was underestimated. The algorithm should be further validated by single primary tumor-derived metastasis treated with the latest comprehensive treatment in diverse populations.

A retrospective study of Pupingqinghua prescription versus Lianhuaqingwen in Chinese participants infected with SARS-CoV-2 Omicron variants.

Background: Coronavirus disease (COVID-19) seriously endangers global public health. Pupingqinghua prescription (PPQH) is an herbal formula from traditional Chinese medicine used for treatment of SARS-CoV-2 infection. This study aims to evaluate the clinical efficacy and safety of PPQH in Chinese participants infected with the SARS-CoV-2 Omicron variant. Methods: A total of 873 SARS-CoV-2 (Omicron)-infected patients were included. Among them, the patients were divided into the PPQH group (653 cases) and LHQW group (220 cases) according to different medications. The effectiveness indicators (hematological indicators, Ct values of novel Coronavirus nucleic acid tests, and viral load-shedding time) and safety indicators (liver and kidney function and adverse events) were analyzed. Results: There was no significant difference in baseline characteristics between the PPQH group and the LHQW group, except the gender; After the treatment, the levels of IL-5, IL-6, IL-10, NK cells, and INF-α of the patients in the PPQH group showed a downward trend (p < 0.05); The viral load shedding time was 5.0 (5.0, 7.0) in the PPQH group and 5.0 (4.0, 7.0) in the LHQW group; both PPQH and LHQW can shorten the duration of symptoms of fever, cough, and sore throat. The re-positive rate of COVID-19 test was 1.5 % in the PPQH group and 2.3 % in the LHQW group. In terms of safety, the levels of γ-GTT decreased significantly (p < 0.01); gastrointestinal reaction was the primary adverse reaction, and the reaction rate was 4.7 % in the PPQH group and 9.5 % in the LHQW group. Conclusion: PPQH can shorten the length of hospital stay and improve clinical symptoms of patients with SARS-COV-2 (Omicron), and it also has a good safety profile.

Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis.

Background: Inadequate lymphangiogenesis is closely related to the occurrence of many kinds of diseases, and one of the important treatments is to promote lymphangiogenesis. Kuoxin Decoction (KXF) is an herbal formula from traditional Chinese medicine used to treat dilated cardiomyopathy (DCM), which is associated with lymphangiogenesis deficiency. In this study, we comprehensively verified whether KXF promotes lymphangiogenesis in zebrafish and in vitro based on network analysis. Methods: We performed virtual screening of the active compounds of KXF and potential targets regarding DCM based on network analysis. Tg (Flila: EGFP; Gata1: DsRed) transgenic zebrafish embryos were treated with different concentrations of KXF for 48 h with or without the pretreatment of MAZ51 for 6 h, followed by morphological observation of the lymphatic vessels and an assessment of lymphopoiesis. RT-qPCR was employed to identify VEGF-C, VEGF-A, PROX1, and LYVE-1 mRNA expression levels in different groups. After the treatment of lymphatic endothelial cells (LECs) with different concentrations of salvianolic acid B (SAB, the active ingredient of KXF), their proliferation, migration, and protein expression of VEGF-C and VEGFR-3 were compared by CCK-8 assay, wound healing assay, and western blot. Results: A total of 106 active compounds were identified constituting KXF, and 58 target genes of KXF for DCM were identified. There were 132 pathways generated from KEGG enrichment, including 5 signaling pathways related to lymphangiogenesis. Zebrafish experiments confirmed that KXF promoted lymphangiogenesis and increased VEGF-C and VEGF-A mRNA expression levels in zebrafish with or without MAZ51-induced thoracic duct injury. In LECs, SAB promoted proliferation and migration, and it could upregulate the protein expression of VEGF-C and VEGFR-3 in LECs after injury. Conclusion: The results of network analysis showed that KXF could regulate lymphangiogenesis through VEGF-C and VEGF-A, and experiments with zebrafish confirmed that KXF could promote lymphangiogenesis. Cell experiments confirmed that SAB could promote the proliferation and migration of LECs and upregulate the protein expression of VEGF-C and VEGFR-3. These results suggest that KXF promotes lymphangiogenesis by a mechanism related to the upregulation of VEGF-C/VEGFR-3, and the main component exerting this effect may be SAB.

The Treatment Status of Patients in NSCLC With RET Fusion Under the Prelude of Selective RET-TKI Application in China: A Multicenter Retrospective Research.

Background: Rearranged during transfection (RET) fusion is a kind of uncommon mutation (about 1%) in non-small cell lung cancer (NSCLC). Although selective tyrosine kinase inhibitors (TKI) (selpercatinib and pralsetinib) have been available, there are no real-world data about the difference in the efficacy between RET-TKI and other regimens in China. Methods: We conducted a multicenter retrospective analysis of 49 patients with RET-fusion-positive NSCLC. The characteristics and the clinical outcomes with RET-TKI, multi-kinase inhibitor (MKI), systematic chemotherapy, and immune-checkpoint inhibitor (ICI)-based regimens were evaluated. Results: Of the 92 treatments in patients included, RET-TKI was administered 24 times (26.1%), systematic chemotherapy was 35 times (38.0%), ICI-based regimens was 26 times (28.3%), and MKI was 7 times (7.6%). RET-TKI had a higher objective response rate than the chemotherapy and ICI-based regimens (63.6% vs. 14.3% vs. 21.0%, p < 0.001). The median progress-free survival (mPFS) of RET-TKI, chemotherapy, immunotherapy, and MKI was 16.9 (95% CI: 1.8-32.0) months, 11.9 (95% CI: 7.7-16.1) months, 6.7 (95% CI: 2.9-10.5) months, and 2.8 (95% CI: 1.1-4.4) months, respectively. The mPFS of RET-TKI was longer than MKI and immunotherapy (p < 0.001), while without difference with chemotherapy (p = 0.096). Moreover, chemotherapy had longer mPFS than MKI (p < 0.001). In subgroup analysis, patients with brain metastases in RET-TKI treatment had worse mPFS than the one of patients without brain metastases (6.1 (95% CI: 0.0-13.9) months and 8.5 (95% CI: 6.3-10.6) months, p = 0.012). For patients having chemotherapy with or without angiogenesis inhibitors, the mPFS was 12.0 (95% CI: 11.05-13.02) months and 9.1 (95% CI: 8.31-9.89) months (p = 0.468). In the group of ICI-based regimens, the expression level of PD-L1 did not affect the mPFS of ICI [PD-L1 (+) vs. PD-L1 (-): 4.7 (95% CI: 1.8-9.0) months vs. 7.6 (95% CI: 1.1-14.0) months, p = 0.910]. For overall patients, ECOG PS score, therapy lines, and therapeutic regimens were the independent factors affecting the prognosis. Conclusions: In RET-fusion-positive NSCLC, RET-TKI is the best choice for a better response rate and PFS. In addition, chemotherapy which may bring a good PFS, is still a good choice for this group of patients.