Neurofibromatosis type 1 with multiple gastrointestinal stromal tumors: A case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is characterized by café-au-lait patches on the skin and the presence of neurofibromas. Gastrointestinal stromal tumor (GIST) is the most common non-neurological tumor in NF1 patients. In NF1-associated GIST, KIT and PDGFRA mutations are frequently absent and imatinib is ineffective. Surgical resection is first-line treatment. CASE SUMMARY: A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass. Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head, face, trunk, and limbs. Her abdomen was soft and nontender. No masses were palpated. Digital rectal examination was unremarkable. Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor. Laparoscopy was performed, which identified eight well-demarcated masses in the jejunum. All were resected and pathologically diagnosed as GISTs. The patient was discharged on day 7 after surgery without complications. No tumor recurrence was evident at the 6-mo follow-up. CONCLUSION: Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.

Development of a prognostic nomogram and risk stratification system for upper thoracic esophageal squamous cell carcinoma.

Background: The study aimed to develop a nomogram model to predict overall survival (OS) and construct a risk stratification system of upper thoracic esophageal squamous cell carcinoma (ESCC). Methods: Newly diagnosed 568 patients with upper ESCC at Fujian Medical University Cancer Hospital were taken as a training cohort, and additional 155 patients with upper ESCC from Sichuan Cancer Hospital Institute were used as a validation cohort. A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS. The predictive power of nomogram model was evaluated by using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). Results: In this study, multivariate analysis revealed that gender, clinical T stage, clinical N stage and primary gross tumor volume were independent prognostic factors for OS in the training cohort. The nomogram based on these factors presented favorable prognostic efficacy in the both training and validation cohorts, with concordance statistics (C-index) of 0.622, 0.713, and area under the curve (AUC) value of 0.709, 0.739, respectively, which appeared superior to those of the American Joint Committee on Cancer (AJCC) staging system. Additionally, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the nomogram presented better discrimination ability to predict survival than those of AJCC staging. Furthermore, decision curve analysis (DCA) of the nomogram exhibited greater clinical performance than that of AJCC staging. Finally, the nomogram fairly distinguished the OS rates among low, moderate, and high risk groups, whereas the OS curves of clinical stage could not be well separated among clinical AJCC stage. Conclusion: We built an effective nomogram model for predicting OS of upper ESCC, which may improve clinicians' abilities to predict individualized survival and facilitate to further stratify the management of patients at risk.

Long-term effect of transurethral partial cystectomy with a 2-micrometer continuous-wave laser for non-muscle-invasive bladder cancer.

Purpose: We have reported the efficacy and safety of 2-micrometer continuous-wave laser cystectomy of non-muscle invasive bladder tumor (NMIBC) (J Urol. 2009;182:66-9). In this study, we evaluated the long-term outcomes of patients with NMIBC who underwent transurethral partial cystectomy with a 2-micrometer continuous-wave laser, and explored the risk factors for tumor recurrence. Methods: This was a retrospective study of patients with NMIBC planned to undergo transurethral partial cystectomy with a 2-micrometer continuous-wave laser at the Fourth Medical Center of the PLA General Hospital between January 2012 and December 2014. The primary outcome was bladder cancer recurrence. Results: A total of 75 patients were enrolled. Sixty-two (82.7%) were male. The patients were 59.8 ± 12.9 years of age. The mean operation time was 38.7 ± 20.4 min. No Clavien grade >2 complications occurred. The duration of catheter indwelling was 3.6 ± 1.8 days. The hospital stay was 6.0 ± 2.3 days. The median follow-up was 80 months. A total of 17 patients had a recurrence during follow-up, and the recurrence-free survival (RFS) rate was 77.3%. In the multivariable analysis, the tumor risk group were independently associated with the recurrence of NMIBC (p = 0.026). Conclusions: After TURBT with a 2-micrometer continuous-wave laser, RFS was 77.3% at the median follow-up of 80 months. All complications were mild. Only tumor risk group was independently associated with the recurrence of NMIBC.

Interlayer-Confined NiFe Dual Atoms within MoS2 Electrocatalyst for Ultra-Efficient Acidic Overall Water Splitting.

Confining dual atoms (DAs) within the van der Waals gap of two-dimensional (2D) layered materials is expected to expedite the kinetic and energetic strength in catalytic process, yet is a huge challenge in atomic-scale precise assembling DAs within two adjacent layers in the 2D limit. Here, an ingenious approach is proposed to assemble DAs of Ni and Fe into the interlayer of MoS2 . While inheriting the exceptional merits of diatomic species, this interlayer-confined structure arms itself with confinement effect, displaying the more favorable adsorption strength on the confined metal active center and higher catalytic activity towards acidic water splitting, as verified by intensive research efforts of theoretical calculations and experimental measurements. Moreover, the interlayer-confined structure also renders metal DAs a protective shelter to survive in harsh acidic environment. Our findings embodied the confinement effects at the atom level, and interlayer-confined assembling of multiple species highlights a general pathway to advance interlayer-confined DAs catalysts within various 2D materials. This article is protected by copyright. All rights reserved.

Preparation and Properties of Polyvinylpyrrolidone/Sodium Carboxymethyl Cellulose Soluble Microneedles.

Transdermal drug delivery is a new means of delivering drugs through the skin to achieve therapeutic effects. Microneedles have several advantages, including low cost, easy self-administration, and high delivery efficiency. Different polymers affect the morphology, mechanical properties, and drug delivery efficiency of microneedles. To study the performance and limitations of microneedles (MNs), we prepared different ratios of polymers. MNs were fabricated from polyvinylpyrrolidone (PVP) and sodium carboxymethyl cellulose (CMC-Na) using the centrifugal molding method. Needle morphology, formability, and other properties of the polymers were evaluated to compare the performances of MNs with different ratios. PVP and CMC-Na were intermixed at different ratios with water as the solvent. The soluble MNs were prepared by mold casting. The morphology, thermodynamic properties, and crystallinity were studied using scanning electron microscopy (SEM), thermogravimetric analysis (TG), differential scanning calorimetric analysis (DSC), and X-ray diffraction (XRD). The results showed that composite microneedles have good thermal stability. Among the different compositions tested, the 10% PVP/2% CMC-Na composite microneedle demonstrated the best performance with a regular surface morphology and relatively high thermal decomposition and melting temperatures. These results indicate that microneedles with appropriate ratios of two different materials possess good formability and other properties.

A New Gnetalean Macrofossil from the Mid-Jurassic Daohugou Formation.

Macrofossil evidence has demonstrated a first radiation of gnetophytes in the Early Cretaceous. However, the origin of the diversity of gnetophytes remains ambiguous because gnetalean macrofossils have rarely been reported from pre-Cretaceous strata. Here, we report a new putative gnetalean macrofossil reproductive shoot which possesses opposite phyllotaxy, long linear leaves more or less decurrent and having a prominent midvein and pedicled ovoid-ellipsoid and longitudinally striated chlamydosperms. Our new fossil is different from other known gnetalean macrofossils in the linear-lanceolate leaves with a midvein and pedicled chlamydosperms. As a result, we describe this new macrofossil reproductive shoot as new to science, i.e., Daohugoucladus sinensis gen. et sp. nov. Our new macrofossil displays additional morphological characters distinct from other known Mesozoic and modern gnetalean species and provides additional evidence of the origin and early evolution of female reproductive organs of gnetophytes.

Co-chaperoning of Chlorophyll and Carotenoid Biosynthesis by ORANGE Family Proteins in Plants.

Chlorophylls and carotenoids are essential photosynthetic pigments. Plants spatiotemporally coordinate the needs of chlorophylls and carotenoids for optimal photosynthesis and fitness in response to diverse environmental and developmental cues. However, how the biosynthesis pathways of these two pigments are coordinated, particularly at posttranslational level to allow rapid control, remains largely unknown. Here, we report that the highly conserved ORANGE (OR) family proteins coordinate both pathways via posttranslationally mediating the first committed enzyme in each pathway. We demonstrate that OR family proteins physically interact with magnesium chelatase subunit I (CHLI) in addition to phytoene synthase (PSY) and concurrently stabilize CHLI and PSY enzymes. We show that loss of OR genes hinders both chlorophyll and carotenoid biosynthesis, limits light-harvesting complex assembly, and impairs thylakoid grana stacking in chloroplasts. Overexpression of OR safeguards photosynthetic pigment biosynthesis and enhances thermotolerance in both Arabidopsis and tomato plants. Our findings establish a novel mechanism by which plants coordinate chlorophyll and carotenoid biosynthesis and provide a potential genetic target to generate climate-resilient crops.

Lipidomic and comparative transcriptomic analysis of fatty acid synthesis pathway in Carya illinoinensis embryo.

Pecan (Carya illinoinensis) is an important oilseed nut and is rich in fatty acids and flavonols. Pecan fatty acid has significantly edible, industrial, and clinical value. To investigate the dynamic patterns and compositions of fatty acid, and the molecular mechanism that controls fatty acid accumulation in pecan, lipidomic and transcriptomic analyses were performed to determine lipid profiles and gene expression in pecan's fatty acid biosynthesis pathway. In the present study, compared to cultivars 'Caddo' and 'Y-01', 'Mahan' formed larger and heavier embryos and accumulated higher oil content. Lipidomic analysis showed that fatty acid and (O-acyl)-1-hydroxy fatty acid contents were higher in 'Mahan' at the mature stage. Based on full-length and comparative RNA-Seq, differential expression gene enrichment analysis revealed that many functional genes participated in the pathways of 'fatty acid biosynthesis', 'fatty acid metabolism', and 'linoleic acid metabolism'. High fatty acid accumulation model from 'Mahan' demonstrated that key enzyme encoding genes played an important role in regulating fatty acid biosynthesis. Co-expression module analysis indicated that several transcription factors (MYB, TCP, bHLH, Dof, ERF, NAC) were involved in fatty acid accumulation by regulating the expression of functional genes, and real-time quantitative PCR verification proved that these transcription factors had a high correlation with pecan fatty acid accumulation pattern. These findings provided an insight into the molecular mechanism of fatty acid accumulation in C. illinoinensis embryo, which contributes to pecan oil yielding and pecan molecular breeding.

Effect of renin-angiotensin-aldosterone system inhibitors on survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Background: Effect of renin-angiotensin-aldosterone system inhibitors (RAASIs) in combination with immune checkpoint inhibitors (ICIs) on prognoses in cancer patients remains controversial. This study systematically evaluated the effect of RAASIs on survival outcomes in cancer patients receiving ICIs treatment and provided an evidence-based reference for the rational use of RAASIs and ICIs combination therapy in clinical practice. Methods: Studies evaluating the prognosis of RAASIs-used versus RAASIs-free in cancer patients receiving ICIs treatment from inception to 1 November 2022 were retrieved by searching PubMed, Cochrane Library, Web of Science, Embase, and major conference proceedings. Studies in English reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS) were included. Statistical analyses were conducted using the software Stata 17.0. Results: A total of 12 studies containing 11739 patients were included, comprising ~4861 patients in the RAASIs-used and ICIs-treated group and ~6878 patients in RAASIs-free and ICIs-treated group. The pooled HR was 0.85 (95%CI, 0.75-0.96; P = 0.009) for OS and 0.91 (95%CI, 0.76-1.09; P = 0.296) for PFS, indicating a positive effect of RAASIs concomitant with ICIs on cancer patients. This effect was observed especially in patients with urothelial carcinoma (HR, 0.53; 95%CI, 0.31-0.89; P = 0.018) and renal cell carcinoma (HR, 0.56; 95%CI, 0.37-0.84; P = 0.005) on OS. Conclusion: Concomitant use of RAASIs and ICIs enhanced the efficacy of ICIs and this combination regimen was associated with significantly improved OS and a trend towards better PFS. RAASIs can be considered as adjuvant drugs when hypertensive patients receive ICIs treatment. Our results provide an evidence-based reference for the rational use of the RAASIs and ICIs combination therapy to improve the efficacy of ICIs in clinical practice. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022372636; https://inplasy.com/, identifier INPLASY2022110136.

Predicting the negative conversion time of nonsevere COVID-19 patients using machine learning methods.

Based on the patient's clinical characteristics and laboratory indicators, different machine-learning methods were used to develop models for predicting the negative conversion time of nonsevere coronavirus disease 2019 (COVID-19) patients. A retrospective analysis was performed on 376 nonsevere COVID-19 patients admitted to Wuxi Fifth People's Hospital from May 2, 2022, to May 14, 2022. The patients were divided into training set (n = 309) and test set (n = 67). The clinical features and laboratory parameters of the patients were collected. In the training set, the least absolute shrinkage and selection operator (LASSO) was used to select predictive features and train six machine learning models: multiple linear regression (MLR), K-Nearest Neighbors Regression (KNNR), random forest regression (RFR), support vector machine regression (SVR), XGBoost regression (XGBR), and multilayer perceptron regression (MLPR). Seven best predictive features selected by LASSO included: age, gender, vaccination status, IgG, lymphocyte ratio, monocyte ratio, and lymphocyte count. The predictive performance of the models in the test set was MLPR > SVR > MLR > KNNR > XGBR > RFR, and MLPR had the strongest generalization performance, which is significantly better than SVR and MLR. In the MLPR model, vaccination status, IgG, lymphocyte count, and lymphocyte ratio were protective factors for negative conversion time; male gender, age, and monocyte ratio were risk factors. The top three features with the highest weights were vaccination status, gender, and IgG. Machine learning methods (especially MLPR) can effectively predict the negative conversion time of non-severe COVID-19 patients. It can help to rationally allocate limited medical resources and prevent disease transmission, especially during the Omicron pandemic.

Application of oncolytic virus in tumor therapy.

Oncolytic viruses (OVs) can selectively kill tumor cells without affecting normal cells, as well as activate the innate and adaptive immune systems in patients. Thus, they have been considered as a promising measure for safe and effective cancer treatment. Recently, a few genetically engineered OVs have been developed to further improve the effect of tumor elimination by expressing specific immune regulatory factors and thus enhance the body's antitumor immunity. In addition, the combined therapies of OVs and other immunotherapies have been applied in clinical. Although there are many studies on this hot topic, a comprehensive review is missing on illustrating the mechanisms of tumor clearance by OVs and how to modify engineered OVs to further enhance their antitumor effects. In this study, we provided a review on the mechanisms of immune regulatory factors in OVs. In addition, we reviewed the combined therapies of OVs with other therapies including radiotherapy and CAR-T or TCR-T cell therapy. The review is useful in further generalize the usage of OV in cancer treatment.

[Mechanism of electroacupuncture penetration needling for relieving synovial inflammation of knee osteoarthritis through TLR4/MyD88/NF-κB signal pathway].

OBJECTIVE: To observe the effects of electroacupuncture (EA) penetration needling on Toll-like receptors 4/myeloid differentiation factor 88/nuclear factor-kappa B (TLR4/MyD88/NF-κB) signaling pathway in rat synovium and the serum-related inflammatory factors, so as to explore the mechanism of EA penetration needling on synovial inflammation in rats with knee osteoarthritis (KOA). METHODS: SD male rats were randomly divided into sham-operation group, model group, EA+penetration needling group, and conventional EA group, with 16 rats in each group. The rats model was prepared by anterior cruciate ligment transection and these rats were forced to exercise for 8 weeks after operation. After successful modeling, in the EA+penetration needling group, the needles were inserted at "Dubi" (ST35) "Neixiyan" (EX-LE4), and at "Xuehai"(SP10) "Liangqiu"(ST34) on the right hind limb, towards each other, 5-8 mm in depth, respectively. In the conventional EA group, the needles were inserted at ST35 and EX-LE4 on the right hind limb, obliquely, at 30° angle to the skin, 3-5 mm in depth; and were inserted at SP10 and ST34 on the right hind limb perpendicularly, 3-5 mm in depth. In these two groups, electric stimulation was operated with dense-disperse wave, 2 Hz/10 Hz in frequency and 0.5-1.5 mA in intensity, retained for 20 min in each treatment. The treatment was given once daily, 10 days as 1 course of treatment, and 2 courses were required at the interval of 2 days. After the intervention, the knee joint effusion was observed by musculoskeletal ultrasound; the contents of IL-1ß, IL-6 and TNF-α in serum were determined by ELISA; the morphological changes in the synovium were observed after H.E. staining; the positive expression of NF-κB p65 in the synovial membrane was detected by immunohistochemical method; the expression levels of TLR4, MyD88, TRAF-6 and NF-κB p65 proteins in the synovial membrane were determined by Western blot. RESULTS: Compared with the sham-operation group, in the model group, the knee joint effusion was obviously increased, the synovial lining cells were distributed irregularly, the cells were disarranged, the pannus was formed largely, and a great number of the inflammatory cells were infiltrated; the contents of serum IL-1ß, IL-6 and TNF-α, the positive expression of NF-κB p65, the protein expression levels of TLR4, MyD88, TRAF-6 and NF-κB p65 in the synovial tissue were increased (P<0.05). Compared with the model group, the knee joint effusion was reduced, the synovial lining cells were proliferated, a small number of the inflammatory cells were infiltrated, and the pannus was formed lightly; the contents of serum IL-1ß, IL-6 and TNF-α, the positive expression of NF-κB p65, the protein expression levels of TLR4, MyD88, TRAF-6 and NF-κB p65 in the synovial tissue were lower (P<0.05) in the EA+penetration needling group and the conventional EA group. In the conventional EA group, the knee joint effusion was increased, the synovial lining cells were proliferated, the inflammatory cells were infiltrated largely, and the pannus was formed increasingly; the contents of serum IL-1ß, IL-6 and TNF-α, and the protein expression levels of TLR4, MyD88 and NF-κB p65 in the synovial tissue were increased when compared with the EA+penetration needling group (P<0.05). CONCLUSION: The EA+penetration needling can significantly relieve the synovial inflammatory reaction and the knee joint effusion in KOA rats. The mechanism is probably related to down-regulating the downstream inflammatory cascade through inhibiting the transduction of TLR4/MyD88/NF-κB signaling pathway.

High-order spatial phase shift method realizes modulation analysis through a single-frame image.

For the modulation-based structured illumination microscopy system, how to obtain modulation distribution with an image has been a research hotspot. However, the existing frequency-domain single-frame algorithms (mainly including the Fourier transform method, wavelet method, etc.) suffer from different degrees of analytical error due to the loss of high-frequency information. Recently, a modulation-based spatial area phase-shifting method was proposed; it can obtain higher precision by retaining high-frequency information effectively. But for discontinuous (such as step) topography, it would be somewhat smooth. To solve the problem, we propose a high-order spatial phase shift algorithm that realizes robust modulation analysis of a discontinuous surface with a single-frame image. At the same time, this technique proposes a residual optimization strategy, so that it can be applied to the measurement of complex topography, especially discontinuous topography. Simulation and experimental results demonstrate that the proposed method can provide higher-precision measurement.

Taxonomic status and nomenclature of Cephalotaxuslanceolata (Cephalotaxaceae).

The nomenclature of Cephalotaxuslanceolata is controversial. After a thorough literature investigation, the nomenclatural problems have been resolved. This name was published in W. C. Cheng et al. (1975) and, although ascribed to "K. M. Feng", there is no suggestion that the descriptive material in the protologue was provided by K. M. Feng. Under Art. 46.5 of the ICN, this name should be attributed to K. M. Feng ex W. C. Cheng et al. but not to K. M. Feng alone. It has been claimed that the name is an illegitimate later homonym of one published by Beissner in 1901, but Beissner never accepted this name in any of his publications and so, under Art. 36.1, he did not validly publish an earlier homonym. Cephalotaxuslanceolatus was first validly published in W. C. Cheng et al. (1975).

Patient-specific approach using data fusion and adversarial training for epileptic seizure prediction.

Epilepsy is the second common neurological disorder after headache, accurate and reliable prediction of seizures is of great clinical value. Most epileptic seizure prediction methods consider only the EEG signal or extract and classify the features of EEG and ECG signals separately, the improvement of prediction performance from multimodal data is not fully considered. In addition, epilepsy data are time-varying, with differences between each episode in a patient, making it difficult for traditional curve-fitting models to achieve high accuracy and reliability. In order to improve the accuracy and reliability of the prediction system, we propose a novel personalized approach based on data fusion and domain adversarial training to predict epileptic seizures using leave-one-out cross-validation, which achieves an average accuracy, sensitivity and specificity of 99.70, 99.76, and 99.61%, respectively, with an average error alarm rate (FAR) of 0.001. Finally, the advantage of this approach is demonstrated by comparison with recent relevant literature. This method will be incorporated into clinical practice to provide personalized reference information for epileptic seizure prediction.

Clinical characteristics and prognosis of non-APAP drug-induced acute liver failure: a large multicenter cohort study.

BACKGROUND: There is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF. METHODS: Patients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients. RESULTS: Regarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p < 0.05), numerically higher than 0.905 of ALFSG-PI but without statistical difference (p > 0.05). These results were successfully validated in the external cohort (147 patients). CONCLUSIONS: Based on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points.

A Surrogate Endpoint for Overall Survival in Locally Advanced and Resectable Esophageal Squamous Cell Carcinoma: a Re-analysis of Data from the NEOCRTEC5010 Trial.

PURPOSE: The study aimed to investigate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) in patients with locally advanced and resectable esophageal squamous cell carcinoma (ESCC). METHODS: We re-analyzed patients' data from the NEOCRTEC5010 randomized clinical trial (RCT; N = 451 patients) to compare their OS with that of an age- and sex-matched cohort from the general population of China. We used expected survival and the standardized mortality ratio (SMR), respectively, in our analysis of data collected from a neoadjuvant chemo-radiotherapy (NCRT) plus surgery group and a surgery-only group. Published data from six RCTs and 20 retrospective studies were used to examine the correlation between DFS and OS at the trial level. RESULTS: The annual hazard rate of disease progression decreased to 4.9% and 8.1% within 3 years in the NCRT and Surgery groups, respectively. Patients who were disease free at 36 months had a 5-year OS of 93.9% (95% CI, 89.7%-98.4%) in the NCRT group with an SMR of 1.1 (95% CI, 0.7-1.8, P = 0.5639). In contrast, the 5-year OS was only 12.9% (95% CI, 7.3% -22.6%) for patients in the NCRT group who exhibited disease progression within 36 months. At the trial level, the DFS and OS were correlated with the treatments' effect (R2 = 0.605). CONCLUSION: Disease free at 36 months (DFS36) is a valid surrogate endpoint for 5-year OS in patients with locally advanced and resectable ESCC. Patients who were disease free at 36 months showed a favorable OS, which was indistinguishable from that of the age- and sex-matched comparison group from the general population; otherwise, their 5-year OS was extremely poor.

Proapoptotic effect of nonthermal pulsed ultrasound on prostate cancer cells in a nude mouse model.

BACKGROUND: Ultrasound (US) can induce cell injury, and we have previously reported that adjusting the pulse repetition frequency (PRF) of ultrasound output can induce prostate cancer cell destruction without causing a rise in the temperature of the irradiated area. In this study, we examined the mechanism of nonthermal ultrasound cell destruction, which was not fully clarified in our previous reports. METHODS: In vitro, we evaluated postirradiation cells immediately after treatment and examined membrane disruption by proliferation assay, LDH assay, and apoptosis assay. In vivo, we injected mice with human LNCaP and PC-3 prostate cancer cells and evaluated the therapeutic effects of US irradiation by H-E staining and immunostaining. RESULTS: Proliferation assays showed inhibition at 3 h postirradiation independently of PRF and cell line (p < 0.05). Quantitative assessment of apoptosis/necrosis by flow cytometry showed widely varying results depending on cell type. LNCaP showed an increase in late apoptosis at 0 h independent of PRF (p < 0.05), while PC-3 showed no significant difference at 0 h. The LDH assay showed an increase in LDH independent of PRF in LNCaP (p < 0.05 respectively), but no significant difference in PC-3. In vivo, tumor volume was compared and a significant reduction was observed at 10 Hz for LNCaP (p < 0.05) and 100 Hz for PC-3 (p < 0.001) at 3 weeks after the start of irradiation. The excised tumors were evaluated with Ki-67, Caspase-3, and CD-31 and showed a significant treatment effect independent of cell type and PRF (p < 0.001 respectively). CONCLUSION: Examining the mechanism behind the therapeutic effect of US irradiation revealed that the main effect was achieved by apoptosis induction rather than necrosis.

Coping with COVID: Performance of China's hierarchical medical system during the COVID-19 pandemic.

Objective: The COVID-19 pandemic has challenged the health system worldwide. This study aimed to assess how China's hierarchical medical system (HMS) coped with COVID-19 in the short-and medium-term. We mainly measured the number and distribution of hospital visits and healthcare expenditure between primary and high-level hospitals during Beijing's 2020-2021 pandemic relative to the 2017-2019 pre-COVID-19 benchmark period. Methods: Hospital operational data were extracted from Municipal Health Statistics Information Platform. The COVID-19 period in Beijing was divided into five phases, corresponding to different characteristics, from January 2020 to October 2021. The main outcome measures in this study include the percentage change in inpatient and outpatient emergency visits, and surgeries, and changing distribution of patients between different hospital levels across Beijing's HMS. In addition, the corresponding health expenditure in each of the 5 phases of COVID-19 was also included. Results: In the outbreak phase of the pandemic, the total visits of Beijing hospitals declined dramatically, where outpatient visits fell 44.6%, inpatients visits fell 47.9%; emergency visits fell 35.6%, and surgery inpatients fell 44.5%. Correspondingly, health expenditures declined 30.5% for outpatients and 43.0% for inpatients. The primary hospitals absorbed a 9.51% higher proportion of outpatients than the pre-COVID-19 level in phase 1. In phase 4, the number of patients, including non-local outpatients reached pre-pandemic 2017-2019 benchmark levels. The proportion of outpatients in primary hospitals was only 1.74% above pre-COVID-19 levels in phases 4 and 5. Health expenditure for both outpatients and inpatients reached the baseline level in phase 3 and increased nearly 10% above pre-COVID-19 levels in phases 4 and 5. Conclusion: The HMS in Beijing coped with the COVID-19 pandemic in a relatively short time, the early stage of the pandemic reflected an enhanced role for primary hospitals in the HMS, but did not permanently change patient preferences for high-level hospitals. Relative to the pre-COVID-19 benchmark, the elevated hospital expenditure in phase 4 and phase 5 pointed to hospital over-treatment or patient excess treatment demand. We suggest improving the service capacity of primary hospitals and changing the preferences of patients through health education in the post-COVID-19 world.