Multiple impacts of the COVID-19 pandemic and antimicrobial stewardship on antimicrobial resistance in nosocomial infections: an interrupted time series analysis.

Objectives: The emergency response to the COVID-19 pandemic may disrupt hospital management activities of antimicrobial resistance (AMR). This study aimed to determine the changing AMR trend over the period in China when stringent COVID-19 response measures were implemented. Methods: This retrospective study was conducted in a designated hospital for COVID-19 patients in Guangzhou, China from April 2018 to September 2021. The prevalence of 13 antimicrobial-resistant bacteria was compared before and after the COVID-19 responses through Chi-square tests. Interrupted time series (ITS) models on the weekly prevalence of AMR were established to determine the changing trend. Controlled ITS models were performed to compare the differences between subgroups. Results: A total of 10,134 isolates over 1,265 days were collected. And antimicrobial-resistant strains presented in 38.6% of the testing isolates. The weekly AMR prevalence decreased by 0.29 percentage point (95% CI [0.05-0.80]) after antimicrobial stewardship (AMS) policy, despite an increase in the prevalence of penicillin-resistant Streptococcus pneumoniae (from 0/43 to 15/43, p < 0.001), carbapenem-resistant Escherichia coli (from 20/1254 to 41/1184, p = 0.005), and carbapenem-resistant Klebsiella pneumoniae (from 93/889 to 114/828, p = 0.042). And the changing trend did not vary by gender (male vs. female), age (<65 vs. ≥65 years), service setting (outpatient vs. inpatient), care unit (ICU vs. non-ICU), the primary site of infection (Lung vs. others), and Gram type of bacteria (positive vs. negative). Conclusion: The response to COVID-19 did not lead to an increase in overall AMR; however, it appears that management strategy on the prudent use of antimicrobials likely contributed to a sizable long-term drop. The frequency of several multidrug-resistant bacteria continues to increase after the COVID-19 epidemic. It is crucial to continue to monitor AMR when COVID-19 cases have surged in China after the relaxation of restriction measures.

Preoperative versus postoperative nonsteroidal anti-inflammatory drugs in femoroacetabular impingement patients undergoing hip arthroscopy surgery: analgesic effect, joint function, patients' satisfaction, and quality of life.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic effects on femoroacetabular impingement (FAI) patients undergoing hip arthroscopy surgery (HAS). However, the influence of medication time on the analgesic effect of NSAIDs is uncertain. This study aimed to compare the analgesic effect, joint function, quality of life (QoL), and patients' satisfaction between preoperative and postoperative NSAIDs in these patients. METHODS: In this prospective, observational study, 165 FAI patients undergoing HAS with NSAIDs (celecoxib, meloxicam, and nimesulide) for analgesia were divided into preoperative (PRE-A) and postoperative analgesia (POST-A) groups according to their actual medication. RESULTS: The visual analog scale (VAS) pain scores on the 1st (P < 0.001) and 3rd (D3) (P = 0.015) days after the operation were lower in the PRE-A group versus the POST-A group but not preoperatively (P = 0.262) or on the 7th day after the operation (D7) (P = 0.302). The proportion of patients receiving rescue analgesia decreased in the PRE-A group versus POST-A group (P = 0.041). However, the modified Harris hip score (mHHS), proportion of patients with an mHHS ≥ 70, and EuroQol-5-dimensional score at preoperative, 1st month (M1), and 3rd month (M3) after the operation were similar between the groups (all P > 0.050). The VAS score on D7 was greater in the PRE-A group compared to the POST-A group (P = 0.014), but the scores at M1 and M3 and the satisfaction and very satisfaction rates at D7, M1, and M3 did not differ between the groups (all P > 0.050). Subgroup analysis revealed that the type of NSAID did not affect most outcomes. CONCLUSION: Preoperative NSAIDs elevate analgesic effect and patients' satisfaction, but not joint function or QoL compared to postoperative NSAIDs in FAI patients undergoing HAS.

Experimental observation of zero-group velocity combined harmonic generated by counter-directional Lamb wave mixing.

In this paper, we present an experimental observation of the phenomenon known as zero-group velocity (ZGV) combined harmonic generation, which is induced by the mixing of counter-directional Lamb waves. We utilize internal resonant conditions to selectively choose the primary mode pair at specific frequencies for the purpose of combined harmonic generation. To detect the ZGV combined harmonic component, we propose a hybrid system that incorporates dual wedge-transducers for generation and a laser interferometric system for receiving. The appearance of the predicted S1-ZGV combined harmonic at a specific mixing frequency is clearly observed in our experiments. Furthermore, we experimentally verify the controllability of the generated combined harmonics induced by the mixing of Lamb waves.

Effects of pay-for-performance based antimicrobial stewardship on antimicrobial consumption and expenditure: An interrupted time series analysis.

Objectives: To evaluate the impact of pay-for-performance on antimicrobial consumption and antimicrobial expenditure in a large teaching hospital in Guangzhou, China. Methods: We collected data from hospital information system from January 2018 through September 2022 in the inpatient wards. Antimicrobial consumption was evaluated using antibiotic use density (AUD) and antibiotic use rate (AUR). The economic impact of intervention was assessed by antimicrobial expenditure percentage. The data was analyzed using interrupted time series (ITS) analysis. Results: Following the implementation of the intervention, immediate decreases in the level of AUD were observed in Department of Hematology Unit 3 (ß = -66.93 DDDs/100PD, P = 0.002), Urology (ß = -32.80 DDDs/100PD, P < 0.001), Gastrointestinal Surgery Unit 3 (ß = -11.44 DDDs/100PD, P = 0.03), Cardiac Surgery (ß = -14.30 DDDs/100PD, P = 0.01), ICU, Unit 2 (ß = -81.91 DDDs/100PD, P = 0.02) and Cardiothoracic Surgery ICU (ß = -41.52 DDDs/100PD, P = 0.05). Long-term downward trends in AUD were also identified in Organ Transplant Unit (ß = -1.64 DDDs/100PD, P = 0.02). However, only Urology (ß = -6.56 DDDs/100PD, P = 0.02) and Gastrointestinal Surgery Unit 3 (ß = -8.50 %, P = 0.01) showed an immediate decrease in AUR, and long-term downward trends in AUR were observed in Pediatric ICU (ß = -1.88 %, P = 0.05) and ICU Unit 1 (ß = -0.55 %, P = 0.02). Conclusion: This study demonstrates that the adoption of pay-for-performance effectively reduces antibiotic consumption in specific departments of a hospital in Guangzhou in the short term. However, it is important to recognize that the long-term impact of such interventions is often limited. Additionally, it should be noted that the overall effectiveness of the intervention across the entire hospital was not significant.

Evaluation of appropriateness of antibiotic prescribing in primary healthcare institutions in China using proxy indicator.

Background: Our objectives were to develop a set of proxy indicators (PIs) suited for assessing antibiotic use appropriateness in China's primary healthcare institutions (PHIs), and assess performance scores of these PIs while exploring factors that influence the antibiotic appropriateness. Methods: We selected potential PIs for the PHIs through a RAND-modified Delphi procedure, and assessed clinimetric properties, focusing on measurability, applicability, and potential for improvement. PIs with favorable clinimetric properties were used to evaluate antibiotic prescription appropriateness by calculating performance scores of each PI. Institutions were categorized into three clusters representing different levels of appropriateness. We used the chi-square test and an ordinal logistic regression model at PHI level to explore factors influencing antibiotic appropriateness. Findings: Eighteen PIs were developed through two rounds of online surveys and one face-to-face meeting involving 20 stakeholders. All PIs met the clinimetric properties criteria and were used to analyze 209,662 antibiotic prescriptions across 269 PHIs. The percentage of PHIs meeting the target ranged from 3.1% to 69.3%, with 6 PIs below 10%. The appropriateness of antibiotic prescriptions was significantly associated with percentages of patients' gender of the PHIs. Interpretation: The varied and suboptimal performance of the PIs indicated the need for diverse efforts to enhance the rational antibiotic use at PHI level. It was necessary to devise distinct sets of PIs for diverse settings in future endeavors. Funding: This work was supported by the National Natural Science Foundation of China (grant numbers 72374009, 81973294).

Hb Guigang [α90 (FG2)Lys→Asn; HBA1:c.273G˃T]: a Novel α-Globin Chain Variant.

BACKGROUND: New hemoglobin (Hb) variants are constantly being updated as assays are developed and the testing population expands. Here, we report a novel Hb variant, named Hb Guigang. METHODS: Hemoglobin (Hb) analysis was analyzed by capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). Glycated hemoglobin was performed by CE and HPLC. Routine genetic analysis was done with Gap-PCR and PCR-reverse dot-blot hybridization. The hemoglobin variant was identified by Sanger sequencing. RESULTS: CE of three cases showed the presence of Hb variants in Zone 5 and Zone 12, respectively. HPLC indicated an elevated P3 peak, suggesting the possible presence of the Hb variant. Hb A1c was measured by CE and HPLC, and the results were 6.7% and 4.76%, respectively. Sanger sequencing confirmed an AAG˃AAT mutation at codon 90 of the HBA1 gene. This mutation was reported for the first time, and we named it Hb Guigang based on the proband's place of residence. CONCLUSIONS: Hb Guigang with normal hematological parameters was separated and quantified by CE, whereas HPLC suggested that Hb Guigang co-eluted with the P3 peaks and could not be quantified.

Real-imaginary spectrum decomposition of the transparency spectra in microwave dressed Rydberg systems.

To distinguish the contributions of electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) in their applications in precision laser spectroscopy, we propose a real-imaginary spectrum decomposition method to investigate the transparency spectra in a four-level microwave (MW) dressed Rydberg system. We show that the opening transparency windows in the absorption spectra of probe field is a prominent character by EIT, EIT-ATS crossover, and ATS when the MW field is turned off and the intensity of the control field is adjusted. When the MW field is turned on and gradually increased, the EIT is destroyed and disappears. In addition, the most prominent characters that open a transparency window are the EIT-ATS crossover and the ATS. Then, if we further increase the intensity of the MW field, we find that the transparency windows open mainly due to the ATS. Compared to the previous considerations of this issue, which were limited to three-level systems, our four-level scheme reported here is useful for understanding the features of quantum interference in multilevel atomic systems, and has potential applications to study enhanced sensitivity, measurement spectroscopic, quantum processing, quantum communication, and transmission.

Spectral Signatures of Vibronic Coupling in Trapped Cold Ionic Rydberg Systems.

Atoms and ions confined with electric and optical fields form the basis of many current quantum simulation and computing platforms. When excited to high-lying Rydberg states, long-ranged dipole interactions emerge which strongly couple the electronic and vibrational degrees of freedom through state-dependent forces. This vibronic coupling and the ensuing hybridization of internal and external degrees of freedom manifest through clear signatures in the many-body spectrum. We illustrate this by considering the case of two trapped Rydberg ions, for which the interaction between the relative vibrations and Rydberg states realizes a quantum Rabi model. We proceed to demonstrate that the aforementioned hybridization can be probed by radio frequency spectroscopy and discuss observable spectral signatures at finite temperatures and for larger ion crystals.

Experimental validation of zero-group-velocity feature guided waves in a welded joint utilizing the pitch-catch measurement technique with air-coupled ultrasonic transducers.

Zero-Group-Velocity (ZGV) Lamb waves in elastic plates had been conducted extensive theoretical and experimental researches in the field of ultrasonic nondestructive testing. The ZGV modes in complex structures had been studied theoretically, but less attention had been paid to their experimental investigation. This paper reports the experimental observation of Zero-Group-Velocity Feature Guided Waves (ZGV-FGWs) in a welded joint using the pitch-catch measurement technique with air-coupled ultrasonic transducers. Firstly, for the elastic plate, it is verified that the received time-domain signal using the pitch-catch measurement method with air-coupled ultrasonic transducers is indeed ZGV Lamb waves. Subsequently, we applied the same pitch-catch measurement method with air-coupled ultrasonic transducers to receive time-domain signals at different excitation frequencies in the welded joint. It is observed that the received time-domain signals in the welded joint oscillate for extended periods of time. By performing short-time Fourier transforms on the received time-domain signals, we analyze the frequency content of the received time-domain signals at different excitation carrier frequencies. By analyzing the spectral amplitude variations of these signals at different excitation carrier frequencies, it can be demonstrated that the spectral amplitude corresponding to the resonance frequency is the largest. These findings collectively affirm that the received time-domain signals in the welded joint exhibit ZGV characteristics, identified as ZGV-FGWs. Consequently, from an experimental perspective, the presence of ZGV-FGWs in the welded joint is verified. Moreover, the experimentally determined resonance frequency of ZGV-FGWs concurs with the results obtained through simulation. This study confirms the feasibility of using the pitch-catch measurement method with air-coupled ultrasonic transducers to excite ZGV-FGWs in a welded joint and provides a reference for future experimental investigations of ZGV-FGWs in complex structures.

Effects of microplastics on the structure and function of bacterial communities in sediments of a freshwater lake.

As an emerging pollutant, microplastics (MPs) cause widespread concern around the world owing to the serious threat they pose to ecosystems. In particular, sediments are thought to be the long-term sink for the continual accumulation of MPs in freshwater ecosystems. Polyethylene (PE) and polyethylene terephthalate (PET) have been frequently detected with large concentration variations in freshwater sediments from the lower reaches of the Yangtze River, one of the most economically developed regions in China, characterized by accelerated urbanization and industrialization, high population density and high plastics consumption. However, the impact of PE and PET on the sedimental bacterial community composition and its function has not been well reported for this specific region. Herein, PE and PET particles were added to freshwater sediments to assess the effects of different MP types on the bacterial community and its function, using three concentrations (500, 1500 and 2500 items/kg) per MP and incubations of 35, 105 and 175 days, respectively. This study identified a total of 68 phyla, 211 classes, 518 orders, 853 families and 1745 genera. Specifically, Proteobacteria, Chloroflexi, Acidobacteriota, Actinobacteriota and Firmicutes were the top five phyla. A higher bacterial diversity was obtained in control sediments than in the MP-treated sediments. The presence of MPs, whether PET or PE, had significant impact on the bacterial diversity, community structure and community composition. PICRUSt2 and FAPOTAX predictions demonstrated that MPs could potentially affect the metabolic pathways and ecologically functional groups of bacteria in the sediment. Besides the MP-related factors, such as the type, concentration and incubation time, the physicochemical parameters had an effect on the structure and function of the bacterial community in the freshwater sediment. Taken together, this study provides useful information for further understanding how MPs affect bacterial communities in the freshwater sediment of the lower reaches of the Yangtze River, China.

Preliminary Study: 3D Nailing for Intertrochanteric Femur Fractures.

Objective: This study introduced the structural features of the Three-Dimensional Proximal Femoral Nail (3DPFN), a patented invention, and highlights its advantages in treating intertrochanteric fractures of the femur. Furthermore, biomechanical comparative experiments validated the biomechanical performance of 3DPFN in treating Evans-Jensen type IV intertrochanteric fractures. Methods: Evans-Jensen type IV intertrochanteric fracture models were created using artificial femurs produced by the American company Sawbone. From January to April 2022, the experimental group was fixed with 3DPFN, while the control group was fixed with the Proximal Femoral Nail Antirotation (PFNA), simulating the loading conditions in the human body. Axial static ultimate pressure tests and dynamic fatigue tests were conducted. The recorded parameters included the maximum load-bearing capacity under axial load, the maximum number of cycles, and the maximum load before failure. Results: Static ultimate pressure tests showed that the static ultimate load in the 3DPFN group was 2532.67±49.20N, whereas in the PFNA group, it was 2240.00±84.35N, with a significant difference between the two groups (P < .05). Dynamic fatigue tests revealed that the maximum number of cycles in the 3DPFN group was 86372.67±4762.59 cycles, while in the PFNA group, it was 8606.67±606.05 cycles, also showing a significant difference (P < .05). Dynamic fatigue tests further indicated that the fatigue limit load before failure in the 3DPFN group was 1664.00±78.27N, whereas in the PFNA group, it was 799.33±63.52N. Again, there was a significant difference between the two groups (P < .05). Conclusion: In both static compression and fatigue tests, 3DPFN exhibits significant biomechanical advantages over PFNA. This suggests that 3DPFN may be an excellent choice for the treatment of intertrochanteric fractures of the femur and holds further research value for development. Future studies may involve clinical trials to validate and refine the 3DPFN design based on the observed results and promote the advancement of orthopedic implant technology.

Morusin inhibits breast cancer-induced osteolysis by decreasing phosphatidylinositol 3-kinase (PI3K)-mTOR signalling.

Bone metastases caused by breast cancer pose a major challenge to the successful treatment of breast cancer patients. Many researchers have suggested that herbal medicines are extremely effective at preventing and treating cancer-associated osteolysis. Previous studies have revealed that Morusin (MOR) is cytotoxic to many cancer cells ex vivo. Nevertheless, how MOR contributes to osteolysis induced by breast cancer is still unknown, and the potential mechanism of action against osteolysis is worthy of further study. The protective effect and molecular mechanism of MOR in inhibiting breast cancer cell-induced osteolysis were verified by experiments and network pharmacology. Cell function was assessed by cell proliferation, osteoclast (OC) formation, bone resorption, and phalloidin staining. Tumour growth was examined by micro-CT scanning in vivo. To identify potential MOR treatments, the active ingredient-target pathway of breast cancer was screened using network pharmacology and molecular docking approaches. This study is the first to report that MOR can prevent osteolysis induced by breast cancer cells. Specifically, our results revealed that MOR inhibits RANKL-induced osteoclastogenesis and restrains the proliferation, invasion and migration of MDA-MB-231 breast cells through restraining the PI3K/AKT/MTOR signalling pathway. Notably, MOR prevented bone loss caused by breast cancer cell-induced osteolysis in vivo, indicating that MOR inhibited the development of OCs and the resorption of bone, which are essential for cancer cell-associated bone distraction. This study showed that MOR treatment inhibited osteolysis induced by breast cancer in vivo. MOR inhibited OC differentiation and bone resorption ex vivo and in vivo and might be a potential drug candidate for treating breast cancer-induced osteolysis.

Ergodicity breaking from Rydberg clusters in a driven-dissipative many-body system.

It is challenging to probe ergodicity breaking trends of a quantum many-body system when dissipation inevitably damages quantum coherence originated from coherent coupling and dispersive two-body interactions. Rydberg atoms provide a test bed to detect emergent exotic many-body phases and nonergodic dynamics where the strong Rydberg atom interaction competes with and overtakes dissipative effects even at room temperature. Here, we report experimental evidence of a transition from ergodic toward ergodic breaking dynamics in driven-dissipative Rydberg atomic gases. The broken ergodicity is featured by the long-time phase oscillation, which is attributed to the formation of Rydberg excitation clusters in limit cycle phases. The broken symmetry in the limit cycle is a direct manifestation of many-body collective effects, which is verified experimentally by tuning atomic densities. The reported result reveals that Rydberg many-body systems are a promising candidate to probe ergodicity breaking dynamics, such as limit cycles, and enable the benchmark of nonequilibrium phase transition.

Hb Hebei [α20 (B1) His→Leu; HBA2:C.62A > T]: A Novel Hemoglobin Variant Found during Measurement of Glycated Hemoglobin.

We report a novel hemoglobin (Hb) variant found in a 34-year-old Chinese male during a routine measurement of glycated hemoglobin. The variant resulted in a P3 peak of 27.5% of the total Hb on high performance liquid chromatography (HPLC) with a glycated hemoglobin mode. However, no abnormal Hb peaks were observed in capillary electrophoresis (CE) with 3.1% Hb A2 and 96.9% Hb A. The amino acid substitution was determined by Sanger sequencing as α20 (B1) His→Leu; the corresponding DNA mutation was identified as CAC > CTC at the first position of codon 20 of the α-chain. This is the first description of the mutation, and we have named it Hb Hebei for the region of origin of the proband.

Predictive Model Construction And Prevention Strategies Of Surgical Site Infection In Laparoscopic Appendectomy.

Objective: To construct a nomogram model for predicting the occurrence of the laparoscopic appendectomy surgical site infection (LASSI) and explore prevention strategies. Methods: A total of 995 patients who underwent laparoscopic appendectomy in Shanxi Bethune Hospital from October 2017 to August 2022 were selected. According to whether there was incision infection within 30 days after operation, the patients were divided into the LASSI (97 cases) and non-LASSI (898 cases) group. The following clinicopathological data from these two groups of patients were collected: gender, age, body mass index, ect. The subjects were randomly divided into training group and verification group according to the 7:3 ratio. Univariate and multivariate analysis was used to screen the related influencing factors and construct a nomogram model to predict the occurrence of LASSI. Rreceiver operating characteristic (ROC) curves and the calibration curve were used to evaluate the predictive value of the model. For patients with LASSI, a more effective preventive measure was explored. Results: Multivariate logistic regression analysis showed that operation time >1h (OR: 1.891; 95% CI: 1.07 to 3.36; P = .029), perforated and gangrenous appendix (OR: 4.078; 95% CI: 1.84 to 9.86; P = .001), free intraperitoneal fluid (OR: 2.836; 95% CI: 1.57 to 5.35; P = .001), BMI>30 kg/m2 (OR: 2.828; 95% CI:1.54 to 5.12; P = .001), diabetes mellitus (DM) (OR: 2.795; 95% CI: 1.54 to 5.28; P = .001) were the independent prognostic factors of LASSI. The prediction nomogram model showed satisfactory performance in predicting the occurrence of LASSI, ROC curve area value of the training and verification groups were respectively 0.753 (95 % CI: 0.688 ~ 0.818) and 0.772 (95 % CI: 0.691-0.852). In the event of LASSI, we took out appendix specimens in sections and sterilized surgical site, which effectively prevented it. Conclusion: This study evaluated the risk factors related to the occurrence of LASSI and established a prediction model for LASSI. The prediction model provides a convenient and fast risk assessment tool for clinicians to predict the occurrence of LASSI. Combined with the newly discovered prevention strategy of segmental removal of appendix and incision disinfection, it can effectively avoid the occurrence of LASSI and potentially reduce the hospitalization time and costs.

Selexipag for the Treatment of Pediatric Pulmonary Hypertension: A Systematic Review.

PURPOSE: To systematically evaluate the safety, dosing regimen, and efficacy of selexipag for pediatric patients with pulmonary hypertension (PH). METHODS: A literature search of the electronic databases of PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar was performed from inception through February 28, 2023. Two reviewers independently searched and evaluated the quality of the studies and pooled data when appropriate. Full-text articles of studies of children diagnosed with PH and treated with selexipag were eligible. Pediatric patients with PH were classified into 2 groups: the add-on therapy group, in which selexipag was used as a third therapy in addition to the baseline treatment, and the transition therapy group, in which patients were switched from parenteral prostacyclin analogs to selexipag. FINDINGS: Fourteen studies involving 58 pediatric patients with PH were included. All studies were either case reports or case series. Overall, 30 and 28 patients were in the add-on and transition therapy groups, respectively. In both groups, selexipag was initially administered as 50-200 µg twice daily and titrated to a tolerated dosage of 200-1,600 µg twice daily. Prostacyclin analogs were simultaneously weaned for patients in the transition group. In the add-on therapy group, 16 patients (80.0%) were at low risk of the World Health Organization functional class (WHO FC I/II), 12 (76.9%) were at low risk of the 6-minute walk distance (6MWD; >350 m), and 21 (95.5%) were at low risk of the pulmonary vascular resistance index (PVRi; <20 WU/m2). Furthermore, N-terminal pro-brain natriuretic peptide and mean pulmonary arterial pressure were significantly improved. More than 70% of patients experienced common tolerable side effects, such as headache, nausea, and diarrhea. In the transition therapy group, 5 patients (55.6%) were at low risk according to WHO FC I/II, 6 (66.7%) were at low risk according to 6MWD, and 14 (87.5) were at low risk according to PVRi; however, selexipag had no significant effect on their hemodynamic parameters. Additionally, more than 80% of patients experienced no side effects. IMPLICATIONS: Selexipag as add-on therapy or for transition from prostacyclin analogs may have a favorable safety profile and potential efficacy for pediatric patients with PH. Further high-quality evidence of the efficacy and safety of selexipag for the treatment of pediatric PH is warranted.

Spinosin inhibits activated hepatic stellate cell to attenuate liver fibrosis by targeting Nur77/ASK1/p38 MAPK signaling pathway.

AIM: Liver fibrosis remains a great challenge in the world. Spinosin (SPI), a natural flavonoid-C-glycoside, possesses various pharmacological activities including anti-inflammatory and anti-myocardial fibrosis effects. In this study, we investigate whether SPI can be a potential lead for the treatment of liver fibrosis and explore whether the orphan nuclear receptor Nur77, a negative regulator of liver fibrosis development, plays a critical role in SPI's action. METHODS: A dual luciferase reporter system of α-SMA was established to evaluate the effect of SPI on hepatic stellate cell (HSC) activation in LX2 and HSC-T6 cells. A mouse model of CCl4-induced liver fibrosis was used to test the efficacy of SPI against liver fibrosis. The expression levels of Nur77, inflammatory cytokines and collagen were determined by Western blotting and qPCR. Potential kinase pathways involved were also analyzed. The affinity of Nur77 with SPI was documented by fluorescence titration. RESULTS: SPI can strongly suppress TGF-ß1-mediated activation of both LX2 and HSC-T6 cells in a dose-dependent manner. SPI increases the expression of Nur77 and reduces TGF-ß1-mediated phosphorylation levels of ASK1 and p38 MAPK, which can be reversed by knocking out of Nur77. SPI strongly inhibits collagen deposition (COLA1) and reduces inflammatory cytokines (IL-6 and IL-1ß), which is followed by improved liver function in the CCl4-induced mouse model. SPI can directly bind to R515 and R563 in the Nur77-LBD pocket with a Kd of 2.14 µM. CONCLUSION: Spinosin is the major pharmacological active component of Ziziphus jujuba Mill. var. spinosa which has been frequently prescribed in traditional Chinese medicine. We demonstrate here for the first time that spinosin is a new therapeutic lead for treatment of liver fibrosis by targeting Nur77 and blocking the ASK1/p38 MAPK signaling pathway.

Expression of CKS2 in Hepatocellular Carcinoma: Correlation with Survival Outcomes and Immune Microenvironment.

Purpose: Cyclin-dependent kinase regulatory subunit 2 (CKS2) has an important function in regulating cancer progression and cell cycle. This research aims to ascertain how CKS2 plays its part through multi-omics analyses, to reveal its relationship with the immune microenvironment in hepatocellular carcinoma (HCC). Material and Methods: Multiple databases were used to determine the transcriptional data of CKS2, epigenetic changes, and effects thereof upon the prognosis of HCC patients. The biological functions of CKS2 in HCC were expounded by functional enrichment analysis. TIMER, GSEA, TIP, and online single-cell sequencing databases were adopted for revealing correlations of CKS2 expression with infiltration of immune cells, immunomodulators, immunity cycle, and immune markers in the immune microenvironment of HCC. In addition, qRT-PCR and Western blot were used to validate gene expression in tissues from HCC patients. Results: Open database analysis confirmed that CKS2 is highly expressed in HCC and that it is related to poor prognosis in HCC patients. Aberrant methylation levels of the two methylation sites of CKS2 in HCC contributed to its high expression and were correlated significantly with survival. The CKS2 expression was positively correlated with most immunomodulators and infiltration levels for B and CD8+T cells, dendritic cells, and macrophages, especially exhausted CD8+T cells. Besides, the CKS2 expression was also found to have significant correlations with immunity cycle steps and diverse immune markers in HCC. The high CKS2 expression was confirmed in HCC at both mRNA and protein levels, showing a significant increase compared to normal tissue. Conclusion: CKS2 is a potential prognostic biomarker of HCC and can promote the progression of HCC via its influences on the immune environment. Additionally, a positive correlation between CKS2 and immune markers was observed, highlighting its potential as an immunotherapeutic target.

Prediction of axillary lymph node metastasis in early breast cancer patients with ultrasonic videos based deep learning.

Objective: To develop a deep learning (DL) model for predicting axillary lymph node (ALN) metastasis using dynamic ultrasound (US) videos in breast cancer patients. Methods: A total of 271 US videos from 271 early breast cancer patients collected from Xiang'an Hospital of Xiamen University andShantou Central Hospitabetween September 2019 and June 2021 were used as the training, validation, and internal testing set (testing set A). Additionally, an independent dataset of 49 US videos from 49 patients with breast cancer, collected from Shanghai 10th Hospital of Tongji University from July 2021 to May 2022, was used as an external testing set (testing set B). All ALN metastases were confirmed using pathological examination. Three different convolutional neural networks (CNNs) with R2 + 1D, TIN, and ResNet-3D architectures were used to build the models. The performance of the US video DL models was compared with that of US static image DL models and axillary US examination performed by ultra-sonographers. The performances of the DL models and ultra-sonographers were evaluated based on accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Additionally, gradient class activation mapping (Grad-CAM) technology was also used to enhance the interpretability of the models. Results: Among the three US video DL models, TIN showed the best performance, achieving an AUC of 0.914 (95% CI: 0.843-0.985) in predicting ALN metastasis in testing set A. The model achieved an accuracy of 85.25% (52/61), with a sensitivity of 76.19% (16/21) and a specificity of 90.00% (36/40). The AUC of the US video DL model was superior to that of the US static image DL model (0.856, 95% CI: 0.753-0.959, P<0.05). The Grad-CAM technology confirmed the heatmap of the model, which highlighted important subregions of the keyframe for ultra-sonographers' review. Conclusion: A feasible and improved DL model to predict ALN metastasis from breast cancer US video images was developed. The DL model in this study with reliable interpretability would provide an early diagnostic strategy for the appropriate management of axillary in the early breast cancer patients.

Quantum sensing of microwave electric fields based on Rydberg atoms.

Microwave electric field (MW E-field) sensing is important for a wide range of applications in the areas of remote sensing, radar astronomy and communications. Over the past decade, Rydberg atoms have been used in ultrasensitive, wide broadband, traceable, stealthy MW E-field sensing because of their exaggerated response to MW E-fields, plentiful optional energy levels and integratable preparation methods. This review first introduces the basic concepts of quantum sensing, the properties of Rydberg atoms and the principles of quantum sensing of MW E-fields with Rydberg atoms. An overview of this very active research direction is gradually expanding, covering the progress of sensitivity and bandwidth in Rydberg atom-based microwave sensing, superheterodyne quantum sensing with microwave-dressed Rydberg atoms, quantum-enhanced sensing of MW E-field and recent advanced quantum measurement systems and approaches to further improve the performance of MW E-field sensing. Finally, a brief outlook on future development directions is provided.