Control of proton transport and hydrogenation in double-gated graphene.

The basal plane of graphene can function as a selective barrier that is permeable to protons1,2 but impermeable to all ions3,4 and gases5,6, stimulating its use in applications such as membranes1,2,7,8, catalysis9,10 and isotope separation11,12. Protons can chemically adsorb on graphene and hydrogenate it13,14, inducing a conductor-insulator transition that has been explored intensively in graphene electronic devices13-17. However, both processes face energy barriers1,12,18 and various strategies have been proposed to accelerate proton transport, for example by introducing vacancies4,7,8, incorporating catalytic metals1,19 or chemically functionalizing the lattice18,20. But these techniques can compromise other properties, such as ion selectivity21,22 or mechanical stability23. Here we show that independent control of the electric field, E, at around 1 V nm-1, and charge-carrier density, n, at around 1 × 1014 cm-2, in double-gated graphene allows the decoupling of proton transport from lattice hydrogenation and can thereby accelerate proton transport such that it approaches the limiting electrolyte current for our devices. Proton transport and hydrogenation can be driven selectively with precision and robustness, enabling proton-based logic and memory graphene devices that have on-off ratios spanning orders of magnitude. Our results show that field effects can accelerate and decouple electrochemical processes in double-gated 2D crystals and demonstrate the possibility of mapping such processes as a function of E and n, which is a new technique for the study of 2D electrode-electrolyte interfaces.

Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post-haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated with impaired cognitive and depressive scores in concentration, short-term memory and verbal memory. This study highlights persistent white matter damage in iTTP patients, potentially contributing to depression and cognitive impairment. Key regions affected include the frontal lobe and cingulate cortex. These findings have significant implications for the acute and long-term management of iTTP, suggesting a need for re-evaluation of treatment approaches during both active phases and remission. Further research is warranted to enhance our understanding of these complexities.

Exploring the structure and hydrogen storage capacity of CeHn0/+ clusters.

The unique 4f orbitals and abundant electronic energy levels of rare earth elements enable effective doping and modification to enhance hydrogen storage performance, making it an increasingly prominent focus of research. The structures of neutral and cationic CeHn0/+ (n = 2-20) clusters have been determined using the Crystal Structure AnaLYsis by Particle Swarm Optimization (CALYPSO) method in conjunction with density functional theory (DFT). Interestingly, the CeH13 and CeH14+ exhibit remarkable stability in the doublet state with Cs and C2v symmetry, respectively. The adsorption energy of CeHn0/+ (n = 2-20) suggests a preference for H atoms to chemically adsorb on Ce atoms. The analysis of molecular orbital composition reveals that the stability of both CeH13 and CeH14+ is attributed to the significant hybridization between the H 1s and Ce 4f orbitals. Both CeH13 and CeH14+ demonstrate significant hydrogen storage capacities, with values reaching 8.5 wt% and 9.1 wt%, respectively.

Prognostic value of the baseline magnetic resonance score in patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy.

AIM: To investigate the prognostic value of the composite posterior circulation Acute Stroke Prognosis Early Computed tomography (CT) Score (ASPECTS)-Collaterals (pcASCO) score, which combines diffusion-weighted imaging (DWI) posterior circulation ASPECTS (pcASPECTS) and the magnetic resonance angiography (MRA)-collateral circulation score at baseline among patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy. MATERIALS AND METHODS: Patients with acute posterior circulation ischaemic stroke who underwent mechanical thrombectomy were analysed retrospectively. The DWI-pcASPECTS and MRA-collateral circulation score before treatment and the modified Rankin Scale (mRS) at 90 days after treatment were used as the endpoints. An mRS ≤2 was defined as a good prognosis, and an mRS ≥3 was defined as a poor prognosis. Multivariate logistic regression was used to analyse independent predictors of functional outcome 90 days after mechanical thrombectomy. RESULTS: Mechanical thrombectomy was performed in 57 patients; 38 patients had a good prognosis, 19 patients had a poor prognosis, and 33 patients were successfully recanalised. Univariate logistic regression found that National Institute of Health Stroke Scale (NIHSS) score (OR: 1.18, p<0.001), pcASPECTS (OR: 1.91, p=0.028) and pcASCO score (OR: 0.51, p=0.001) were factors of good functional outcome. Receiver operating characteristic curve (ROC curve) analysis showed that the diagnostic efficiency of the NIHSS and pcASCO was better (AUC = 0.88, 0.83, p<0.05) than that of the pcASPECTS (AUC = 0.65). The prediction model was established by age, NIHSS, and pcASCO, and the diagnostic efficiency of the prediction model was better (AUC = 0.94). CONCLUSIONS: The composite MR-pcASCO score can be used as an important predictor of the prognosis of patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy.

Indocyanine green near-infrared fluorescence-assisted video endoscopic inguinal lymph node dissection for rectal cancer: a single-center experience.

BACKGROUND: This study aimed to investigate the safety and feasibility of indocyanine green near-infrared fluorescence (ICG-NIR) fluorescence-guided video-endoscopic inguinal lymphadenectomy (VEIL) for rectal cancer with inguinal lymph node metastasis (ILNM). METHODS: A retrospective analysis was conducted on 11 patients with rectal cancer who underwent ICG-NIR fluorescence-guided VEIL, assessing various parameters such as operation time, intraoperative bleeding, number of harvested lymph nodes, intraoperative and postoperative complications, and follow-up. RESULTS: Regarding surgical procedures for ILNM, unilateral surgery was performed in 7 cases (54.5%) and bilateral surgery in 4 cases (45.5%). Among these 15 ICG-NIR-guided VEIL surgeries in 11 patients, positive fluorescence visualization was achieved in 13 operations (86.7%). The median estimated blood loss was 10 ml, and the median operation time was 90 min. One case (6.7%) required conversion to open surgery. The median duration of the drain tube was 12 days, and the median length of postoperative hospital stay was 20 days. Postoperative complications were observed, including incisional infection in 2 cases (18.2%), lymphatic leakage in 5 cases (45.5%), urinary infection in 1 case (9.1%), and pneumonia in 3 cases (27.3%). Complications such as skin necrosis, lower limb venous thrombosis, lower limb swelling, or impaired movement were observed during the postoperative follow-up period. No cases of primary lesion, groin, or pelvic lymph node recurrence were observed. CONCLUSION: ICG-NIR fluorescence-guided VEIL is a safe and feasible surgical treatment for rectal cancer with ILNM. ICG fluorescence guidance holds promise as a more personalized and precise approach for VEIL in rectal cancer surgery.

Cryo-storage of porcine hides at the industrial scale for tissue engineering and regenerative medicine application.

BACKGROUND: The industrial scale cryo-storage of raw tissue materials requires a robust, low-cost and easy-to-operate method that can facilitate the down-stream process. OBJECTIVE: The study was aimed to develop the multifunctional protective solutions (MPS) for transportation at ambient conditions and also subsequent cryo-storage below -20 degree C of raw porcine hides for tissue engineering and regenerative medicine. MATERIALS AND METHODS: Protective solutions with antimicrobial activity and proteinase-inhibiting activity were developed and tested for its efficacy in preserving the extracellular matrix of porcine dermis from microbial spoilage, proteolytic degradation, freeze damage and excessive dehydration during shipping and cryo-storage. The MPSs contained phosphate-buffered saline with ethylene diamine tetra acetic acid (EDTA) added as chelator and proteinase inhibitor, as well as glycerol or maltodextrin (M180) as cryoprotectants. RESULTS: MPSs prepared with EDTA and glycerol or M180 had significant antimicrobial activity and proteinase-inhibiting activity during the period of shipping and handling. Glycerol and M180 prevented eutectic salt precipitation and excessive freeze dehydration upon cryo-storage of porcine hides. Without glycerol or M180, hides could be freeze-dehydrated to the low hydration at ~0.4 g/g dw, and formed irreversible plications after freezing. A critical hydration (0.8~0.9 g/g dw) was observed for the extracellular matrix of porcine dermis, and dehydration to a lower level could impose enormous stress and potential damage. The soaking of porcine hides in MPSs decreased water content as glycerol and M180 entered into dermis. Upon equilibration, the glycerol content in the tissue was about 94% of the incubating glycerol solution, but the M180 content in the tissue was only about 50% of the incubating M180 solution, indicating that M180 did not get into the entire aqueous domain within dermis. MPSs reduced ice formation and increased the unfrozen water content of porcine raw hides upon cryo-storage. CONCLUSION: MPSs prepared with EDTA and glycerol or M180 have antimicrobial activity and proteinase-inhibiting activity, which can be used for transportation and cryo-storage of raw hides at the industrial scale. Glycerol at 7.5% w/v and M180 at 20% w/v were sufficient to prevent freeze damage and excessive freeze dehydration. Doi.org/10.54680/fr24310110312.

Viscoelastic properties of decellularized and freeze-dried human dermis between i909c and 40cC.

BACKGROUND: Human donor skin is processed to make the acellular dermis matrix (ADM) for tissue repair and regeneration. There is no data on the viscoelastic properties of ADM at room and subzero temperatures. OBJECTIVE: The work evaluated the temperature dependence of viscoelastic properties of freeze-dried ADM. MATERIALS AND METHODS: Donor skin was de-epidermized, de-cellularized and freeze-dried with trehalose as the lyo-protectant. Glass transition of freeze-dried ADM was measured by differential scanning calorimeter (DSC), and viscoelastic properties were examined by dynamic mechanical analyzer (DMA). RESULTS: At the low moisture range (1.4 +/- 0.5%), the glass transition temperature (Tg) of freeze-dried ADM was 90 degree C to 100 degree C. As the moisture content increased, the Tg decreased steadily. At the high moisture range (10.8 +/- 2.9%), the Tg was 40 degree C to 60 degree C. There were large donor-to-donor variations in viscoelastic properties of freeze-dried ADM as demonstrated by the changes in storage modulus (G'), loss modulus (G") and damping factor tan delta (G"/G'). However, the trends of the temperature dependence for G', G" and tan delta were similar among all 8 donors. For each donor, changes in G' and G" were relatively small between -90 degree C and 40 degree C, and G' was at least one order of magnitude greater than G". Two viscoelastic relaxations were observed in freeze-dried ADM, one at -20 degree C and the other at -60 degree C respectively. CONCLUSION: Freeze-dried ADM was protected in the glassy carbohydrate matrix. DMA observed two viscoelastic relaxations (i.e., alpha process at -20 degree C and beta process at -60 degree C). Overall changes in G' and G'' of freeze-dried ADM were relatively small within one order of magnitude between -90 degree C and 40 degree C. https://doi.org/10.54680/fr24110110612.

Chinese university students' help-seeking behaviors when faced with mental health challenges.

BACKGROUND: Mental illnesses and mental health challenges have become increasingly pervasive among Chinese university students. However, the utilization rate of mental health services is low among students. AIMS: We aimed to explore Chinese university students' help-seeking behaviors to understand how they deal with mental health challenges and use the results to inform the development of effective mental health promotion initiatives. METHODS: In this study, we conducted 13 focus group interviews with students in six universities in Jinan, China, including 91 (62%) female students and 56 (38%) male students. We drew on the Theory of Planned Behaviors to guide our thematic analysis to gain a contextual understanding of participants' accounts on help-seeking. RESULTS: Our results have depicted the help-seeking patterns of Chinese university students and show that there are four major behaviors which are self-reliance, seeking support from peers and families, seeking professional support, and accessing virtual mental health care. CONCLUSION: Results from this study can be used to inform the development of mental health literacy programming for students in universities that share similar contexts, and the study has also opened up a new space for using qualitative approaches to study mental health needs and access to care in diverse populations.

[Effects of pelvic-abdominal mechanics exercises during pregnancy on improving perinatal pelvic floor function in primiparous women].

Objective: To explore the effects of pelvic-abdominal mechanics exercises during pregnancy on improving pelvic floor function in primiparous women during the perinatal period. Methods: A single-center prospective study selected 200 primipara of singleton pregnancies with prenatal care and delivery established at Shanghai Tongren hospital from June 2022 to June 2023 as the study subjects. Participants were divided into two groups: the exercise group (100 cases) and the control group (100 cases) by using a random number table method, five participants dropped out of the study due to reasons such as follow-up failure. Ultimately, the exercise group consisted of 97 cases, while the control group consisted of 98 cases. Participants who engaged in pelvic-abdominal mechanics exercises for at least 3 months, exercising once a week, were included in the exercise group. Those who did not engage in exercise were included in control group. Comparing the two groups in terms of pregnancy discomfort symptoms, delivery outcomes, postpartum pelvic floor electromyography results, postpartum quality of life, and pelvic floor disease incidence. The statistical methods utilized included independent t-test, Pearson chi-square test, Fisher's exact test, and Mann-Whitney U test. Results: In the late stage of pregnancy, the VAS score for low back pain was 5.05±1.22 in the exercise group and 5.47±1.55 in the control group, with a statistically significant difference (t=2.090, P<0.05). The PFDI-20 score was 23.33±8.41 in the exercise group and 25.76±8.34 in the control group, with a statistically significant difference (t=2.026, P<0.05). The PFIQ-7 score was 19.21±7.69 in the exercise group and 26.66±6.19 in the control group, with a statistically significant difference (t=6.851, P<0.05). There was no statistically significant difference in sleep quality and incidence of urinary incontinence between the two groups in late pregnancy (t=1.252, P=0.396, P>0.05). In terms of childbirth outcomes, the exercise group had a vaginal delivery rate of 81.44% (79 cases), while the control group had a rate of 64.28% (63 cases), with a statistically significant difference (χ2=9.022, P<0.05). The duration of the second stage of labor was (42.68±21.38) minutes in the exercise group and (50.54±21.33) minutes in the control group, with a statistically significant difference (t=2.178, P<0.05). At 42 days postpartum, the evaluation of pelvic floor function showed that the vaginal pressure in the exercise group was 62.19±10.04, while in the control group it was 52.68±15.55, with a statistically significant difference (t=-5.074, P<0.05). The MOS grading in the exercise group was 3.82±1.26, whereas in the control group it was 2.34±1.55, with a statistically significant difference (t=-7.355, P<0.05). In terms of the incidence of postpartum pelvic floor disorders, the occurrence of pelvic organ prolapse was 7.22% in the exercise group and 12.24% in the control group, with no statistically significant difference (χ2=1.402, P>0.05). The occurrence rate of stress urinary incontinence was 13.4% in the exercise group and 30.61% in the control group, with a statistically significant difference (P=0.015, P<0.05). Conclusion: Pelvic-abdominal mechanics exercises may have some advantages in reducing symptoms related to perinatal pelvic floor dysfunction, enhancing pelvic floor function, and preventing the occurrence of pelvic floor disease.

[Expression of DARS2 in colorectal cancer and its clinical significance].

Objective: To investigate the expression of DARS2 and its clinical significance in colorectal cancer. Methods: In this study, bioinformatics tools, especially gene expression profile interactive analysis 2 (GEPIA2), were used to conduct an in-depth analysis of DARS2 expression in colorectal cancer tissues. Immunohistochemical staining was carried out in 108 colorectal cancer specimens and 30 normal colorectal tissues obtained from the First Affiliated Hospital of Nanchang University, Nanchang, China. Colorectal cancer cell lines (HCT116 and SW480) were transfected with small interfering RNA (siRNA) and DARS2 overexpression plasmid to examine the effects of DARS2 knockdown and overexpression on cell function. To assess the effects on cell function, CCK8 and transwell migration assays were used to assess proliferation and cell motility, respectively. Additionally, protein immunoblotting was employed to scrutinize the expression of proteins associated with the epithelial-mesenchymal transition of colorectal cancer cells. Results: DARS2 exhibited a pronounced upregulation in expression within colorectal cancer tissues compared to their normal epithelial counterparts. Furthermore, DARS2 expression was higher in colorectal cancer of stage Ⅲ-Ⅳ than those of stage Ⅰ-Ⅱ, exhibiting a significant correlation with N staging, M staging, and pathological staging (P<0.05). Kaplan-Meier analyses showed a decreased overall survival rate in colorectal cancer with DARS2 expression compared to those without DARS2 expression (P<0.05). In the siRNA transfection group, there was a significant reduction in cell proliferation and migration (P<0.01 and P<0.05, respectively). Conversely, the transfection of DARS2 overexpression plasmids substantially increased both cell proliferation and migration (P<0.05). Additionally, immunoblotting revealed that DARS2 knockdown led to an upregulation of E-cadherin expression and a downregulation of N-cadherin and vimentin expression. In contrast, DARS2 overexpression resulted in increased N-cadherin and vimentin expression, coupled with reduction in E-cadherin expression. Conclusions: There is a strong association between DARS2 expression and colorectal cancer progression. Silencing DARS2 inhibits cell proliferation and migration, exerting a discernible influence on the epithelial-mesenchymal transition process.

[Pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus: a case report].

Nocardia is a rarely encountered opportunistic gram-positive bacterium that exhibits marked invasiveness and dissemination. Typically, acquired through trauma or inhalation, this pathogen primarily affects immunocompromised individuals and is a potentially life-threatening risk in severe cases. Nocardia otitidiscaviarum is a particularly rare subtype of Nocardia infection, and the occurrence of concurrent Aspergillus infection is extremely rare. In cases where both infections manifest concomitantly, rapid and accurate diagnosis is essential to facilitate the subsequent selection of appropriate anti-infective interventions. This paper reported the diagnostic and therapeutic experience in managing a case of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. The patient presented with an acute onset, rapid progression, and early manifestation of respiratory failure. The diagnostic process included respiratory pathogen culture and bronchoscopy, which was supplemented with targeted next-generation sequencing (tNGS). These comprehensive diagnostic modalities led to the identification of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. After adjustment of the antibiotic regimen, the patient's condition improved rapidly, culminating in a timely discharge.

[An analysis of disease burden of occupational lung cancer in China from 1990 to 2019].

Objective: To analyze the trend of disease burden, including mortality and disability-adjusted life years (DALYs) , of occupational lung cancer in China from 1990 to 2019. Methods: In June 2022, the data of occupational lung cancer was obtained from Global Burden of Disease Study 2019 (GBD) . Excel summarized the data, and the mortality rate, DALYs and age-normalized rate were analyzed. Applying Joinpoint Regression Program software annual Percentage Change (APC) and Average Annual Percentage Change Rate (AAPC) . Results: Age-standardized mortality rates ranged from 2.41 in 1990 to 3.14 per 100 000 in 2019, with gender differences and a positive correlation with age. DALYs increased from 580, 000 person-years in 1990 to 1 509 900 person-years in 2019. The rate of standardized DALYs increased from 63.03 per 100 000 in 1990 to 71.65 per 100 000 in 2019. According to the annual percentage change (APC) analysis by Joinpoint Regression Program software, the age-normalized mortality and DALY rates decreased from 2011 to 2016, and the increasing trend from 2016 to 2019 was significantly lower than that before 2011. And the increase at this stage was not statistically significant. The APCC values of mortality rate, standardized mortality rate, DALYs rate and changed DALYs rate were 3.28, 0.92, 2.64 and 0.44, respectively, and the trend differences were statistically significant. Conclusion: The disease burden of occupational lung cancer is increasing from 1990 to 2019. Lung cancer screening should be carried out among high-risk populations to achieve early diagnosis and treatment.

Unequivocal Identification of Spin-Triplet and Spin-Singlet Superconductors with Upper Critical Field and Flux Quantization.

Spin-triplet superconductors play central roles in Majorana physics and quantum computing but are difficult to identify. We show the methods of kink-point upper critical field and flux quantization in superconducting rings can unequivocally identify spin-singlet, spin-triplet in centrosymmetric superconductors, and singlet-triplet admixture in noncentrosymmetric superconductors, as realized in γ-BiPd, ß-Bi_{2}Pd, and α-BiPd, respectively. Our findings are essential for identifying triplet superconductors and exploring their quantum properties.

Multi-dimensional radiomics analysis to predict visceral pleural invasion in lung adenocarcinoma of ≤3 cm maximum diameter.

AIM: To explore the value of radiomics analysis in preoperatively predicting visceral pleural invasion (VPI) of lung adenocarcinoma (LAC) with ≤3 cm maximum diameter and to compare the performance of two-dimensional (2D) and three-dimensional (3D) computed tomography (CT) radiomics models. MATERIALS AND METHODS: A total of 391 LAC patients were enrolled retrospectively, of whom 142 were VPI (+) and 249 were VPI (-). Radiomics features were extracted from 2D and 3D regions of interest (ROIs) of tumours in CT images. 2D and 3D radiomics models were developed combining the optimal radiomics features by using the logistic regression machine-learning method and radiomics scores (rad-scores) were calculated. Nomograms were constructed by integrating independent risk factors and rad-scores. The performance of each model was evaluated by using the receiver operator characteristic (ROC) curve, decision curve analysis (DCA), clinical impact curve (CIC), and calculating the area under the curve (AUC). RESULTS: There was no difference in the VPI prediction between 2D and 3D radiomics models (training group: 2D AUC=0.835, 3D AUC=0.836, p=0.896; validation group: 2D AUC=0.803, 3D AUC=0.794, p=0.567). The 2D and 3D nomograms performed similarly regarding discrimination (training group: 2D AUC=0.867, 3D AUC=0.862, p=0.409, validation group: 2D AUC=0.835, 3D AUC=0.827, p=0.558), and outperformed their corresponding radiomics models and the clinical model. DCA and CIC revealed that the 2D nomogram had slightly better clinical utility. CONCLUSION: The 2D radiomics model has a similar discrimination capability compared with the 3D radiomics model. The 2D nomogram performs slightly better for individual VPI prediction in LAC.

Application of B-flow imaging and its enhanced mode in perforator mapping.

AIM: To explore the value of B-flow (B-mode blood flow) imaging and its enhanced mode in perforator mapping. MATERIALS AND METHODS: Before surgery, B-flow imaging, enhanced B-flow imaging, colour Doppler flow imaging (CDFI), and contrast-enhanced ultrasound (CEUS) were used to detect the skin-perforating vessels and small vessels in the fat layer of the donor site. Taking the intra-operative results as the reference standard, the diagnostic consistency and efficiency of the four modes were compared. Statistical analysis was performed using the Friedman M-test, Cochran's Q-test, and the Z-test. RESULTS: Thirty flaps were excised, with 34 skin-perforating vessels and 25 non-skin-perforating vessels, as confirmed during surgery. In order of the number of skin-perforating vessels detected, the results showed that enhanced B-flow imaging detected more vessels than B-flow imaging and CDFI (all p<0.05), CEUS detected more vessels than B-flow imaging and CDFI (all p<0.05), B-flow imaging detected more vessels than CDFI (p<0.05). All four modes had remarkable and satisfactory diagnostic consistency and effectiveness, but B-flow imaging was the best (sensitivity 100%, specificity 92%, Youden index 0.92). In order of the number of small vessels in the fat layer detected, the results showed that enhanced B-flow imaging detected more vessels than CEUS, B-flow imaging, and CDFI (all p<0.05). CEUS detected more vessels than B-flow imaging and CDFI (all p<0.05). CONCLUSION: B-flow imaging is an alternative method for perforator mapping. Enhanced B-flow imaging can reveal the microcirculation of flaps.

Age-related adiposity and beta-cell function: impact on prediabetes and diabetes prevalence in middle-aged and older Han Chinese adults.

PURPOSE: To investigate the effect of aging on the prevalence of prediabetes and diabetes, and the influence of aging on the associations among adipose mass, redistribution, ß cell function, and the prevalence of hyperglycaemia. METHOD: This urban-based cross-sectional study included 1033 Chinese Han people, aged 40-65 years. The abdominal subcutaneous fat area (SFA) and visceral fat area (VFA) were determined by magnetic resonance imaging. The prevalence rates of prediabetes and diabetes were analyzed according to age group (40-49, 50-59, and 60-65 years). The effects of aging on abdominal fat mass, adipose distribution, insulin action indexes were also assessed. RESULTS: Prediabetes and diabetes prevalence gradually increased with age. Both SFA and VFA increased, while SFA/VFA decreased, in the 50-59 and 60-65 years age groups compared to the 40-49 years group. Homeostatic model assessment of insulin resistance (HOMA-IR) increased with fat mass. Homeostatic model assessment of beta-cell function (HOMA-ß) and early-phase insulin secretion (∆I30/∆G30) were decreased in the 60-65 years group compared to the younger age groups. Increased age, VFA, and HOMA-IR, as well as decreased HOMA-ß, were risk factors for the development of prediabetes and diabetes. The associations between central obesity and the development of prediabetes and diabetes, but not the associations of SFA/VFA, HOMA-IR, and HOMA-ß with hyperglycaemia prevalence, weakened with age. CONCLUSIONS: The prevalence of prediabetes and diabetes increased with age. Central obesity may be related stronger to the development of hyperglycaemia in younger people.

[The 500th case: pain in both hip joints, headache, and diplopia].

A male child, aged 5 years and 3 months, was admitted to the Oncology Department with a history of pain in both hip joints, headache, and diplopia lasting for 40 days. Physical examination did not reveal definitive signs or obvious abnormalities in the nervous system. Imaging studies showed only abnormalities in the craniocerebrum and spinal cord. Routine cerebrospinal fluid (CSF) analysis revealed elevation in the total number of white blood cells, mainly mononuclear cells. Biochemical analysis of CSF showed normal glucose and chloride levels, and increased protein concentrations. The possibility of central nervous system (CNS) infection was initially considered. Subsequently, antibacterial and antiviral therapy was administered; however, this treatment was ineffective. Further examination of CSF through immunophenotyping revealed mature B-cell lymphoma with CNS involvement; there were no neoplastic lesions detected elsewhere in the body. Thus, the patient was diagnosed with primary central nervous system lymphoma (PCNSL). Complete remission was achieved after chemotherapy with the CNCL-2017-mature B-cell lymphoma regimen. Thus far, all chemotherapy cycles have been completed, the patient remains in complete remission, and the follow-up is ongoing. Clinicians should pay close attention to PCNSL in children.

[Investigate of the etiology and prevention status of liver cirrhosis].

Objective: To investigate the etiology, prevention and treatment status, and their corresponding regional differences of the patients with liver cirrhosis in China, in order to provide scientific basis for the development of diagnosis and control strategies in China. Methods: Clinical data of patients diagnosed with liver cirrhosis for the first time through January 1, 2018 to December 31, 2020 from 50 hospitals in seven different regions of China were collected and analyzed retrospectively, and the difference of etiology, treatment, and their differences in various regions were analyzed. Results: A total of 11 861 cases with liver cirrhosis were included in the study. Thereinto, 5 093 cases (42.94%) were diagnosed as compensated cirrhosis, and 6 768 cases (57.06%) had decompensated cirrhosis. Notably, 8 439 cases (71.15%) were determined as chronic hepatitis B-caused cirrhosis, 1 337 cases (11.27%) were alcoholic liver disease, 963 cases (8.12%) were chronic hepatitis C, 698 cases (5.88%) were autoimmune liver disease, 367 cases (3.09%) were schistosomiasis, 177 cases (1.49%) were nonalcoholic fatty liver, and 743 cases (6.26%) of other types of liver disease. There were significant differences in the incidence of chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, fatty liver, schistosomiasis liver disease, and autoimmune liver disease among the seven regions (P<0.001). Only 1 139 cases (9.60%) underwent endoscopic therapy, thereinto, 718 cases (6.05%) underwent surgical therapy, and 456 cases (3.84%) underwent interventional therapy treatment. In patients with compensated liver cirrhosis, 60 cases (0.51%) underwent non-selective ß receptor blockers(NSBB), including 59 cases (0.50%) underwent propranolol and 1 case (0.01%) underwent carvedilol treatment. In patients with decompensated liver cirrhosis, 310 cases (2.61%) underwent NSBB treatment, including 303 cases (2.55%) underwent propranolol treatment and 7 cases (0.06%) underwent carvedilol treatment. Interestingly, there were significant differences in receiving endoscopic therapy, interventional therapy, NSBB therapy, splenectomy and other surgical treatments among the seven regions (P<0.001). Conclusion: Currently, chronic hepatitis B is the main cause (71.15%) of liver cirrhosis in several regions of China, and alcoholic liver disease has become the second cause (11.27%) of liver cirrhosis in China. The three-level prevention and control of cirrhosis in China should be further strengthened.

[Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation].

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

[Perivascular epithelioid cell tumor of the lung: a clinicopathological analysis of eight cases].

Objective: To investigate the clinicopathological features of perivascular epithelioid cell tumor (PEComa) of the lung. Methods: Eight PEComa cases of the lung diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China from July 2008 to December 2021 were collected and subject to immunohistochemical staining, fluorescence in situ hybridization and next generation sequencing. The relevant literature was reviewed and the clinicopathological features were analyzed. Results: There were 5 males and 3 females, aged from 18 to 70 years (mean 39 years). There were 3 cases of the right upper lung, 3 cases of the left lower lung, 1 case of the left upper lung and 1 case of the right middle lung. Seven cases were solitary and 1 case was multifocal (4 lesions). Seven cases were benign while one was malignant. The tumors were all located in the peripheral part of the lung, with a maximum diameter of 0.2-4.0 cm. Grossly, they were oval and well circumscribed. Microscopically, the tumor cells were oval, short spindle-shaped, arranged in solid nests, acinar or hemangiopericytoma-like patterns, with clear or eosinophilic cytoplasm. The stroma was rich in blood vessels with hyalinization. Coagulated necrosis and high-grade nuclei were seen in the malignant case, and calcification was seen in 2 cases. Immunohistochemically, the tumor cells were positive for Melan A (8/8), HMB45 (7/8), CD34 (6/8), TFE3 (4/7), and SMA (3/8). All cases were negative for CKpan and S-100. TFE3 (Xp11.2) gene fusion was examined using the TFE3 break-apart fluorescence in situ hybridization in 5 cases, in which only the malignant case was positive. The next generation sequencing revealed the SFPQ-TFE3 [t(X;1)(p11.2;p34)] fusion. Follow-up of the patients ranged from 12 to 173 months while one patient was lost to the follow-up. The malignant case had tumor metastasis to the brain 4 years after the operation and then received radiotherapy. Other 6 cases had no recurrence and metastasis, and all the 7 patients survived. Conclusions: Most of the PEComas of the lung are benign. When there are malignant morphological features such as necrosis, high-grade nuclei or SFPQ-TFE3 gene fusion, close follow-up seems necessary.