Accurately computing the electronic properties of a quantum ring.

A promising approach to study condensed-matter systems is to simulate them on an engineered quantum platform1-4. However, the accuracy needed to outperform classical methods has not been achieved so far. Here, using 18 superconducting qubits, we provide an experimental blueprint for an accurate condensed-matter simulator and demonstrate how to investigate fundamental electronic properties. We benchmark the underlying method by reconstructing the single-particle band structure of a one-dimensional wire. We demonstrate nearly complete mitigation of decoherence and readout errors, and measure the energy eigenvalues of this wire with an error of approximately 0.01 rad, whereas typical energy scales are of the order of 1 rad. Insight into the fidelity of this algorithm is gained by highlighting the robust properties of a Fourier transform, including the ability to resolve eigenenergies with a statistical uncertainty of 10-4 rad. We also synthesize magnetic flux and disordered local potentials, which are two key tenets of a condensed-matter system. When sweeping the magnetic flux we observe avoided level crossings in the spectrum, providing a detailed fingerprint of the spatial distribution of local disorder. By combining these methods we reconstruct electronic properties of the eigenstates, observing persistent currents and a strong suppression of conductance with added disorder. Our work describes an accurate method for quantum simulation5,6 and paves the way to study new quantum materials with superconducting qubits.

Alcohol-associated liver disease-Global epidemiology.

Alcohol-associated liver disease (ALD), as highlighted in this narrative review, is a major public health concern, increasingly impacting global disease burden and premature mortality. In 2019, ALD accounted for the loss of 11 million life-years worldwide. The rising number of deaths and disability-adjusted life-years attributed to ALD, particularly pronounced in the United States, are alarming. Projections suggest that the economic impact of ALD, as seen in the United States, could potentially double by 2040. ALD is increasingly prevalent among younger adults (20-45 y) and has become the leading cause of liver transplantation in both United States and Europe. During the COVID-19 pandemic, the existing trend was further amplified as high-risk drinking patterns coincided with a rise in hospital admissions for alcohol-associated hepatitis and increased ALD-related mortality. The prevalence of ALD is estimated at 3.5% in the general population, 26.0% among hazardous drinkers, and 55.1% among those with alcohol use disorders. Alarmingly, 5-year mortality rates for patients with ALD exceed 50%, with even higher rates in more advanced disease stages. Methodological challenges, such as underreporting, diagnostic difficulties, and variability in registry data quality, complicate the accurate assessment of the impact of ALD. Additionally, the contribution of alcohol to the progression of other liver diseases is often under acknowledged in health care registries, leading to a significant underestimation of its broader implications for liver health. Addressing the growing ALD concern requires robust public health initiatives, heightened awareness, refined diagnostic techniques, and comprehensive epidemiological studies. These measures are vital to tackle the increasing prevalence of ALD and mitigate its extensive impact on individuals and health care systems.

Unveiling the temperature-dependent thermoelectric properties of the undoped and Na-doped monolayer SnSe allotropes: a comparative study.

Motivated by the excellent thermoelectric (TE) performance of bulk SnSe, extensive attention has been drawn to the TE properties of the monolayer SnSe. To uncover the fundamental mechanism of manipulating the TE performance of the SnSe monolayer, we perform a systematic study on the TE properties of five monolayer SnSe allotropes such asα-,ß-,γ-,δ-, andε-SnSe based on the density functional theory and the non-equilibrium Green's functions. By comparing the TE properties of the Na-doped SnSe allotropes with the undoped ones, the influences of the Na doping and the temperature on the TE properties are deeply investigated. It is shown that the figure of meritZTwill increase as the temperature increases, which is the same for almost all the Na-doped and undoped cases. The Na doping can enhance or suppress theZTin different SnSe allotropes at different temperatures, implying the presence of the anomalous suppression of theZT. The Na doping inducedZTsuppression may be caused basically by the sharp decrease of the power factor and the weak decrease of the electronic thermal conductance, rather than by the decrease of the phononic thermal conductance. We hope this work will be able to enrich the understanding of the manipulation of TE properties by means of dimensions, structurization, doping, and temperature.

Head-to-head comparison of prostate-specific membrane antigen positron emission tomography/computed tomography and multiparametric magnetic resonance imaging in the detection of biochemical recurrence of prostate cancer: a systematic review and meta-analysis.

AIM: Our main goal of this meta-analytical analysis was to evaluate the diagnostic effectiveness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) against multiparametric magnetic resonance imaging (mpMRI) in the context of identifying biochemical recurrence in patients with prostate cancer (PCa). MATERIALS AND METHODS: A thorough search covering articles published until March 2023 was carried out across major databases such as PubMed, Embase, and Web of Science. Studies examining the direct comparison of PSMA PET/CT and mpMRI in patients with PCa suffering biochemical recurrence were included in the inclusion criteria. Using the renowned Quality Assessment of Diagnostic Performance Studies-2 technique, each study's methodological rigor was assessed. RESULTS: We analyzed data from six eligible studies involving 290 patients in total. The combined data showed that for PSMA PET/CT and mpMRI, respectively, the pooled overall detection rates for recurrent PCa after definitive treatment were 0.69 (95% confidence interval [CI]: 0.45-0.89) and 0.70 (95% CI: 0.44-0.91). The detection rates for local recurrence were specifically 0.52 (95% CI: 0.39-0.65) and 0.62 (95% CI: 0.31-0.89), while they were 0.50 (95% CI: 0.26-0.74) and 0.32 (95% CI: 0.18-0.48) for lymph node metastasis. Notably, there was no discernible difference between the two imaging modalities in terms of the overall detection rate (P = 0.95). The detection rates for local recurrence and lymph node metastasis did not differ statistically significantly (P = 0.55, 0.23). CONCLUSION: The performance of PSMA PET/CT and mpMRI in identifying biochemical recurrence in PCa appears to be comparable. However, the meta-analysis' findings came from research with modest sample sizes. In this context, more extensive research should be conducted in the future.

[The clinical significance of lateral pelvic sentinel lymph node biopsy using indocyanine green fluorescence navigation in laparoscopic lateral pelvic lymph node dissection].

Objectives: This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs). Methods: The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit). Results: All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively. Conclusions: This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.

[Efficacy analysis of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 inhibitor treatment in hormone receptor positive/human epidermal growth factor receptor 2-low metastatic breast cancer].

Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] (P<0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance (P=0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95%CI: 4.3-5.7) and 4.0 (95%CI: 1.6-6.4) months, respectively, with no statistical significance (P=0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95%CI: 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 1.8-2.2) months] (P<0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95%CI: 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 0.6-3.4) months] (P=0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.

[Association between CD4+T lymphocyte and body composition with physical frailty among elderly HIV-infected patients in Chongqing City].

Objective: To identify the association between CD4+T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods: From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition. Results: The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×107 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [OR (95%CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [OR (95%CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group (Pinteraction<0.05). Conclusion: The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

[SRSF2 promotes glioblastoma cell proliferation by inducing alternative splicing of FSP1 and inhibiting ferroptosis].

Objective: To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells. Methods: The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis. Results: SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals (P<0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA (P<0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased (P<0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged (P>0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion: SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.

[Adjuvant therapy strategies for breast cancer based on the efficacy of neoadjuvant therapy].

With the advent of the precision cancer therapy era, neoadjuvant therapy has become the standard therapy for certain types of breast cancer. Neoadjuvant therapy is a fundamental treatment plan implemented at the time of disease diagnosis, and its efficacy can guide the formulation of subsequent adjuvant therapy strategies. Building on the efficacy of neoadjuvant therapy and medication regimens, in conjunction with evidence-based medicine and healthcare policy, developing adjuvant therapy strategies for breast cancer following neoadjuvant therapy has the benefit of providing more precise treatment options for patients.

[Comparing the impact of left bundle branch area pacing and traditional left ventricular pacing on right heart function following dual-chamber pacemaker implantation].

Objective: To compare the effects of left bundle branch area pacing (LBBaP) versus traditional right ventricular pacing (RVP) on left ventricular function in patients after dual-chamber pacemaker implantation. Methods: A retrospective cohort study was conducted on patients who underwent dual-chamber pacemaker implantation from March 2017 to April 2021 in Beijing Anzhen Hospital. The patients were divided into the LBBaP group and RVP group based on the placement of the ventricular lead. Follow-up was conducted until March 2022, comparing baseline and follow-up echocardiographic parameters, pacing parameters, and the incidence and timing of complications between the two groups. The complications included ventricular electrode perforation, dislocation, pericardial effusion, tricuspid valve perforation, etc. Results: A total of 163 patients aged (68.3±13.5) years were included, including 82 (50.3%) men, with 80 patients in the LBBaP group and 83 in the RVP group. Baseline left ventricular end-diastolic diameter ((50.49±4.95) mm vs. (47.43±8.15) mm, P=0.01) and left atrium (LA) ((33.14±5.94) mm vs. (30.18±3.92) mm, P=0.001) in the LBBaP group were significantly higher than those in the RVP group. Follow-up LA diameter ((37.10±6.70) mm vs. (40.10±8.90) mm, P=0.016) showed a statistically significant difference in the LBBaP group compared to the RVP group. There was no statistically significant difference between the two groups in baseline QRS duration(P=0.490). Postoperative QRS duration in the LBBaP group was significantly lower ((110.69±24.01) ms vs. (139.65±29.85) ms, P<0.010). Intraoperative threshold in the LBBaP group was significantly higher ((0.83±0.32) V/0.48 ms vs. (0.71±0.23) V/0.48 ms, P=0.004), while impedance was lower ((754.53±205.59) Ω vs. (905.41±302.75) Ω, P<0.01). Comparing with the RVP group, postoperative ventricular pacing ratio (VP) ((87.39±20.92) % vs. (79.49±25.76) %, P=0.034), threshold ((0.90±0.38) V/0.48 ms vs. (0.69±0.27) V/0.48 ms, P<0.01) in the LBBaP group were higher, and impedance ((507.45±77.37) Ω vs. (620.52±197.29) Ω, P<0.01) in the LBBaP group was lower. Postoperative follow-up period was 5 to 51 months, with a median follow-up time of 17 months. No statistically significant difference in overall complications between the LBBaP and RVP groups was found (13.8% (11/80) vs. 7.2% (6/83), P>0.05). The median time to occurrence of complications after surgery was significantly earlier in the LBBaP group (29.74 (95%CI 27.21-32.26) months vs. 46.17 (95%CI 42.48-49.86) months, P=0.030). Conclusion: LBBaP demonstrates more stable pacing parameters, substantial improvement in clinical left ventricular function, with a relatively higher threshold compared to traditional RVP, and complications occurs relatively early.

Lipoprotein Z, a hepatotoxic lipoprotein, predicts outcome in alcohol-associated hepatitis.

BACKGROUND AND AIMS: Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation. APPROACH AND RESULTS: We measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay. Serum levels of LP-Z were significantly elevated in four AH cohorts compared with control groups, including heavy drinkers and patients with cirrhosis. We defined a Z-index, calculated by the ratio of LP-Z to total apolipoprotein B-containing lipoproteins, representing the degree of deviation from normal VLDL metabolism. A high Z-index was associated with 90-day mortality independent from the Model for End-Stage Liver Disease (MELD) and provided added prognosticative value. Both a Z-index ≤ 0.6 and a decline of Z-index by ≥0.1 in 2 weeks predicted 90-day survival. RNA-sequencing analyses of liver tissues demonstrated an inverse association in the expression of enzymes responsible for the extrahepatic conversion of VLDL to LDL and AH disease severity, which was further confirmed by the measurement of serum enzyme activity. To evaluate whether the FC in LP-Z could contribute to the pathogenesis of AH, we found significantly altered FC levels in liver explant of patients with AH. Furthermore, FC in reconstituted LP-Z particles caused direct toxicity to human hepatocytes in a concentration-dependent manner, supporting a pathogenic role of FC in LP-Z. CONCLUSIONS: Impaired lipoprotein metabolism in AH leads to the accumulation of LP-Z in the circulation, which is hepatotoxic from excessive FC. A Z-index ≤ 0.6 predicts 90-day survival independent from conventional biomarkers for disease prognostication.

Spin-dependent thermoelectric transport properties of Cr-doped blue phosphorene.

We systematically investigate the thermoelectric (TE) properties of the Cr-doped blue phosphorene (blue-P) along the armchair and zigzag directions. First, we find the semiconducting band structure of the blue-P will become spin-polarized due to the Cr-doping, and can be seriously changed by the doping concentration. Then we show the Seebeck coefficient, the electronic conductance, the thermal conductance, and the figures of meritZTs are all dependent on the transport directions and doping concentration. However, two pairs of the peaks of the charge and spinZTs can be always observed with the low-height (high-height) pair on the side of the negative (positive) Fermi energy. In addition, at temperature 300 K the extrema of the charge (spin)ZTs of the blue-P along the two directions are kept to be larger than 22 (90) for the different doping concentrations and will be further enhanced at lower temperature. Therefore, we believe the Cr-doped blue-P should be a versatile high-performance TE material which may be used in the fields of the thermorelectrics and spin caloritronics.

Electronic structures, transport properties, and optical absorption of bilayer blue phosphorene nanoribbons.

Based on first-principles density functional theory and nonequilibrium Green's function, we study the electronic band structures, the electronic transport properties, and the optical absorption of bilayer blue phosphorene nanoribbons (BPNRs). Both bilayer armchair BPNRs (a-BPNRs) and zigzag BPNRs (z-BPNRs) behave as semiconductors in the narrow nanoribbon case and metals in the wide nanoribbon case, sharply different from their monolayer counterparts where the monolayer a-BPNRs (z-BPNRs) are always semiconducting (metallic). This indicates that interlayer couplings or the increasing layer number may induce the switching of the conductivity of the monolayer BPNRs, which is absent in graphene and phosphorene nanoribbons. Furthermore, we explore the edge states of the energy bands near Fermi energy, and find that there are almost no pure edge-state band branches in the bilayer BPNRs, which can be attributed to the interlayer couplings between the edge-states in one layer and the bulk-states in the other. Consequently, the resulting complex band structures cannot be directly analyzed any more in the framework of the two-body coupling picture just according to the simple band structures of the monolayer BPNRs. Finally, we present the current-voltage characteristics and the optical absorption of the bilayer a-BPNRs and z-BPNRs. The influences of the nanoribbon width and the interlayer couplings on the current and the anisotropic optical absorption can be understood based on the complex energy band structures. This research should be an important reference of extending the field of BPNRs from the monolayer to the bilayer case, and deepen the understanding of the difference between the monolayer and bilayer nanoribbons in different materials.

Circulating Citrate Is Associated with Liver Fibrosis in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is associated with mitochondrial damage. Circulating mitochondrial metabolites may be elevated in NAFLD but their associations with liver damage is not known. This study aimed to assess the association of key mitochondrial metabolites with the degree of liver fibrosis in the context of NAFLD and nonalcoholic steatohepatitis (NASH). Cross-sectional analyses were performed on two cohorts of biopsy-proven NAFLD and/or NASH subjects. The association of circulating mitochondrial metabolite concentrations with liver fibrosis was assessed using linear regression analysis. In the single-center cohort of NAFLD subjects (n = 187), the mean age was 54.9 ±13.0 years, 40.1% were female and 86.1% were White. Type 2 diabetes (51.3%), hypertension (43.9%) and obesity (72.2%) were prevalent. Those with high citrate had a higher proportion of moderate/significant liver fibrosis (stage F ≥ 2) (68.4 vs. 39.6%, p = 0.001) and advanced fibrosis (stage F ≥ 3) (31.6 vs. 13.6%, p = 0.01). Citrate was associated with liver fibrosis independent of age, sex, NAFLD activity score and metabolic syndrome (per 1 SD increase: ß = 0.19, 95% CI: 0.03-0.35, p = 0.02). This association was also observed in a cohort of NASH subjects (n = 176) (ß = 0.21, 95% CI: 0.07-0.36, p = 0.005). The association of citrate with liver fibrosis was observed in males (p = 0.005) but not females (p = 0.41). In conclusion, circulating citrate is elevated and associated with liver fibrosis, particularly in male subjects with NAFLD and NASH. Mitochondrial function may be a target to consider for reducing the progression of liver fibrosis and NASH.

[Targeting microRNA-125b inhibited the metastasis of Alisertib resistance cells through mediating p53 pathway].

Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and ß-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.

[A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer].

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

[The predictive value of microvascular obstruction for adverse left ventricular remodeling after primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a prospective study].

Objectives: Microvascular obstruction (MVO) is a specific cardiac magnetic resonance (CMR) imaging feature in patients with acute myocardial infarction. The purpose of this study was to elucidate the predictive value of MVO in left ventricular adverse remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (STEMI). Methods: A total of 167 patients with STEMI undergoing primary PCI in the Chinese PLA General Hospital from 2016 to 2020 were enrolled in this prospective cohort study, the average age of study patients was 57±10 years old, with 151 males (90.4%) and 16 females (9.6%). The patients were divided into the MVO group (n=81) and non-MVO group (n=86) according to the presence or absence of MVO on CMR imaging, respectively. The primary endpoint of the study was the occurrence of left ventricular adverse remodeling, which was defined as an increase in left ventricular end diastolic volume (LVEDV) by >20% at 6 months after primary PCI compared with the baseline. Patients who completed follow-up were diagnosed as left ventricular adverse remodeling or no left ventricular adverse remodeling according to CMR. The baseline data, perioperative data, and related data of end points were compared between the MVO group and non-MVO group. Finally, the predictive value of MVO in left ventricular adverse remodeling was calculated by receiver operating characteristic curve analysis. Results: In the baseline data, preoperative thrombolysis in myocardial infarction (TIMI) flow (χ2=13.74, P=0.003) and postoperative TIMI flow (χ2=14.87, P=0.001) were both obviously decreased in the MVO group. After 6 months of follow-up, the incidence of left ventricular adverse remodeling in the MVO group was significantly higher than that in the non-MVO group [37.0%(27/73) vs. 18.9%(14/74), χ2=5.96, P=0.015]. The left ventricular end systolic volume at 6 months post infarction in the MVO group was significantly larger than that in the non-MVO group [(94±32) vs. (68±20) ml, t=-5.98, P<0.001], as well as the LVEDV [(169±38) vs. (143±29) ml, t=-4.74, P<0.001]. Receiver operating characteristic curve showed that the area under the curve of MVO size for predicting left ventricular adverse remodeling was 0.637. Conclusion: The risk of left ventricular adverse remodeling is significantly increased in patients with MVO after primary PCI for acute STEMI.

[Rediscussion on hot issues of endocrine therapy for breast cancer].

In the past decade, generated data of large-scale clinical research of endocrine therapy and the update of guidelines have changed clinical practice of breast cancer treatment. However, there are unresolved issues on endocrine therapy. Based on new evidences and clinical experience, we expounded our points on neoadjuvant endocrine therapy, CDK4/6 inhibitoradjuvant therapy, concepts of endocrine sensitivity and endocrine resistance, first-line treatment for metastatic breast cancer, treatment options after progression on CDK4/6 inhibitor and treatment ofvisceral crisis.

[Expert consensus on endocrine therapy of breast cancer (2023 edition)].

Endocrine therapy is the primary systemic therapy for hormone receptor-positive breast cancer, which runs through the whole process of treatment for early and metastatic breast cancer. The development of new endocrine agents and targeted drugs such as cyclin-dependent kinases 4/6(CDK4/6)inhibitors has improved outcome of patients with hormone receptor-positive breast cancer and changed the treatment landscape. The update of clinical research data provides more treatment options, calling for treatment optimization. Experts had a deep discussion around the hot topics on endocrine therapy of breast cancer, and formulated the'Expert consensus on endocrine therapy of breast cancer (2023 edition)'.This consensus is based on research data worldwide and clinical practice experience, with the aims of standardizing clinical diagnosis and optimizing treatment in neoadjuvant, adjuvant and metastatic setting of hormone receptor-positive breast cancer.

[Pathogenic characterization of Klebsiella pneumoniae resistant to carbapenems and polymyxin].

Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.