[Establishment of a prognostic nomogram and discussion on optimal treatment for cervical adenocarcinoma:a retrospective study based on SEER database and Chinese single-center data].

Objective: To establish and validate a predicting nomogram for cervical adenocarcinoma based on surveillance, epidemiology and end results (SEER) database and Chinese single-center data, and to explore the optimal treatment for cervical adenocarcinoma. Methods: This study selected 2 478 cervical adenocarcinoma patients from the SEER database as the training cohort, and 195 cervical adenocarcinoma patients from Cancer Hospital of Dalian University of Technology, Liaouing Cancer Hospital and Institute as an external validation cohort. Clinicopathological information and follow-up data of the two cohorts were collected. The radiotherapy group was defined as receiving comprehensive treatment based on concurrent chemoradiotherapy after initial diagnosis, while the surgery group was defined as receiving comprehensive treatment based on radical surgery. Log-rank test and cox regression were used to evaluate factors affecting the prognosis of cervical adenocarcinoma patients. A nomogram was drawn to predict the 3-year and 5-year overall survival rates of cervical adenocarcinoma patients, and then internal validation of the training cohort from SEER database and external validation of the hospital cohort were conducted. Results: (1) In the SEER database training cohort, there were 385 patients (15.54%, 385/2 478) in the radiotherapy group and 2 093 patients (84.46%, 2 093/2 478) in the surgery group. Overall survival time of the radiotherapy group was (55.8±51.3) months, while that of the surgery roup was (94.4±61.7) months, the difference between the two groups was statistically significant (χ2=256.44, P<0.001). Log-rank test showed that age, marital status, maximum of tumor diameters, pathological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and treatments were all significant factors affecting the overall survival time of cervical adenocarcinoma patients (all P<0.001). Multivariate Cox regression analysis showed that elder (>50 years old), single status, huge tumors (>4 cm), high pathological grades (G2, G3), and advanced FIGO stages (≥Ⅱa2 stage) were independent risk factors for the overall survival time of cervical adenocarcinoma patients (all P<0.05); compared with radiotherapy, surgery was a protective factor for the prognosis of cervical adenocarcinoma patients (HR=0.619, 95%CI: 0.494-0.777; P<0.001). Further analysis of locally advanced stage and Ⅲc stage of patients showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm (HR=0.414, 95%CI: 0.182-0.942; P=0.036) in locally advanced stage and Ⅲc T1 to T2 stage (HR=0.473, 95%CI: 0.307-0.728; P=0.001). (2) The external validation cohort consisted of 39 patients (20.00%, 39/195) in the radiotherapy group and 156 patients (80.00%, 156/195) in the surgery group. The overall survival time of patients in the radiotherapy group was (51.7±34.3) months, while that of the surgery group was (63.1±26.6) months (χ2=28.41, P<0.001). Further analysis was conducted on locally advanced stage and Ⅲc stage patients, and multivariate Cox regression analysis was performed after propensity score matching, which showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm in locally advanced stage (HR=0.141, 95%CI: 0.023-0.843; P=0.032) and Ⅲc T1 to T2 stage (HR=0.184, 95%CI: 0.036-0.947; P=0.043). (3) Establishment and internal and external validation of nomogram: based on the six factors screened out by the multivariate Cox regression model, the nomogram was developed to predict the prognosis of cervical adenocarcinoma patients. The consistency index of the internal and external validation were 0.801 and 0.766, respectively, and the calibration curves matched well with the ideal fitting line. Conclusions: The key to the treatment of cervical adenocarcinoma is to prioritize radical surgery for patients with conditions for radical tumor resection. Compared with concurrent chemoradiotherapy, patients with locally advanced stages (Ⅰb3, Ⅱa2), and Ⅲc (T1, T2) stages cervical adenocarcinoma could benefit from comprehensive treatment based on radical surgery. The nomogram of this study has been validated internally and externally, and show good survival prediction efficacy for cervical adenocarcinoma patients.

Spatiotemporal Evolution of Developing Palate in Mice.

The intricate formation of the palate involves a series of complex events, yet its mechanistic basis remains uncertain. To explore major cell populations in the palate and their roles during development, we constructed a spatiotemporal transcription landscape of palatal cells. Palate samples from C57BL/6 J mice at embryonic days 12.5 (E12.5), 14.5 (E14.5), and 16.5 (E16.5) underwent single-cell RNA sequencing (scRNA-seq) to identify distinct cell subsets. In addition, spatial enhanced resolution omics-sequencing (stereo-seq) was used to characterize the spatial distribution of these subsets. Integrating scRNA-seq and stereo-seq with CellTrek annotated mesenchymal and epithelial cellular components of the palate during development. Furthermore, cellular communication networks between these cell subpopulations were analyzed to discover intercellular signaling during palate development. From the analysis of the middle palate, both mesenchymal and epithelial populations were spatially segregated into 3 domains. The middle palate mesenchymal subpopulations were associated with tooth formation, ossification, and tissue remodeling, with initial state cell populations located proximal to the dental lamina. The nasal epithelium of the palatal shelf exhibited richer humoral immune responses than the oral side. Specific enrichment of Tgfß3 and Pthlh signals in the midline epithelial seam at E14.5 suggested a role in epithelial-mesenchymal transition. In summary, this study provides high-resolution transcriptomic information, contributing to a deeper mechanistic understanding of palate biology and pathophysiology.

[Use of the ETV6/RUNX1 probe to verify the performance of the fluorescence in situ hybridization probe before clinical detection].

Objective: To explore the standardized performance of a FISH probe before clinical detection. Methods: The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test. Results: The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001. Conclusion: For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

Narrow bandwidth, low-emittance positron beams from a laser-wakefield accelerator.

The rapid progress that plasma wakefield accelerators are experiencing is now posing the question as to whether they could be included in the design of the next generation of high-energy electron-positron colliders. However, the typical structure of the accelerating wakefields presents challenging complications for positron acceleration. Despite seminal proof-of-principle experiments and theoretical proposals, experimental research in plasma-based acceleration of positrons is currently limited by the scarcity of positron beams suitable to seed a plasma accelerator. Here, we report on the first experimental demonstration of a laser-driven source of ultra-relativistic positrons with sufficient spectral and spatial quality to be injected in a plasma accelerator. Our results indicate, in agreement with numerical simulations, selection and transport of positron beamlets containing N e + ≥ 10 5 positrons in a 5% bandwidth around 600 MeV, with femtosecond-scale duration and micron-scale normalised emittance. Particle-in-cell simulations show that positron beams of this kind can be guided and accelerated in a laser-driven plasma accelerator, with favourable scalings to further increase overall charge and energy using PW-scale lasers. The results presented here demonstrate the possibility of performing experimental studies of positron acceleration in a laser-driven wakefield accelerator.

[Preliminary study on the effect of Echinococcus multilocaris on phenotypic transformations of glucose metabolism and polarization types in macrophages].

OBJECTIVE: To investigate the effects of Echinococcus multilocularis on the phenotypic transformations of glucose metabolism, polarization types and inflammatory responses in macrophages, so as to provide insights into elucidation of echinococcosis pathogenesis. METHODS: Bone marrow cells were isolated from C57BL/6J mice at ages of 6 to 8 weeks, and induced into bone marrow-derived macrophages (BMDMs) with mouse macrophage colony-stimulating factor (M-CSF), which served as controls (BMDMs-M0). BMDMs-M0 induced M2 macrophages by interleukin-4 for 24 hours served as the IL-4 induction group, and BMDMs-M0 co-cultured with 2.4 ng/mL E. multilocularis cystic fluid (CF) served as the BMDM-CF co-culture group, while BMDMs-M0 co-cultured with E. multilocularis protoscolex (PSC) at a ratio of 500:1 served as the BMDM-PSC co-culture group. The types of polarization of BMDMs co-cultured with E. multilocularis CF and PSC were analyzed using flow cytometry, and the expression of macrophage markers, inflammatory factors, and glucose metabolism-related enzymes was quantified using fluorescent quantitative real-time PCR (qPCR) and Western blotting assays. RESULTS: There were significant differences among the four groups in terms of Arginase-1 (Arg1) (F = 1 457.00, P < 0.000 1), macrophages-derived C-C motif chemokine 22 (Ccl22) (F = 22 203.00, P < 0.000 1), resistin-like α (Retnla) (F = 151.90, P < 0.000 1), inducible nitric oxide synthase (iNOS) (F = 107.80, P < 0.001), hexokinase (HK) (F = 9 389.00, P < 0.000 1), pyruvate kinase (PK) (F = 641.40, P < 0.001), phosphofructokinase 1 (PFK1) (F = 43.97, P < 0.01), glucokinase (GK) (F = 432.50, P < 0.000 1), pyruvate dehydrogenase kinases1 (PDK1) (F = 737.30, P < 0.000 1), lactic dehydrogenase (LDH) (F = 3 632.00, P < 0.000 1), glucose transporter 1 (GLUT1) (F = 532.40, P < 0.000 1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (F = 460.00, P < 0.000 1), citrate synthase (CS) (F = 5 642.00, P < 0.01), glycogen synthase1 (GYS1) (F = 273.30, P < 0.000 1), IL-6 (F = 1 823.00, P < 0.000 1), IL-10 (F = 291.70, P < 0.000 1), IL-1ß (F = 986.60, P < 0.000 1), and tumor necrosis factor (TNF)-α (F = 334.80, P < 0.000 1) and transforming growth factor (TGF)-ß mRNA expression (F = 163.30, P < 0.001). The proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-PSC co-culture group [(22.87% ±1.48%) vs. (1.70% ±0.17%); t = 24.61, P < 0.001], and the proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-CF co-culture group [(20.07% ±0.64%) vs. (1.93% ±0.25%); t = 45.73, P < 0.001]. The mRNA expression of M2 macrophages markers Arg1, Ccl22 and Retnla was significantly higher in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01), and no significant difference was seen in the mRNA expression of the M1 macrophage marker iNOS among the three groups (P > 0.05), while qPCR assay quantified higher mRNA expression of key glycolytic enzymes HK, PK and PFK, as well as inflammatory factors IL-10, IL-1ß, TNF-α and TGF-ß in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01). Western blotting assay determined higher HK, PK and PFK protein expression in the BMDM-PSC co-culture group than in the control group (all P values < 0.05), and qPCR quantified higher GLUT1, GAPDH and IL-6 mRNA expression in the BMDM-CF co-culture group than in the control group (all P values < 0.05), while higher HK, PK and PFK protein and mRNA expression (all P values < 0.01), as well as lower IL-6 and TNF-α and higher TGF-ß mRNA expression (both P values < 0.05) was detected in the IL-4 induction group than in the control group. Glycolytic stress test showed no significant difference in the extracellular acidification rate (ECAR) of mouse BMDM among the control group, IL-4 induction group and BMDM-PSC co-culture group (F = 124.4, P < 0.05), and a higher ECAR was seen in the BMDM-PSC co-culture group and a lower ECAR was found in the IL-4 induction group than in the control group (both P values < 0.05). CONCLUSIONS: Treatment of E. multilocularis CF or PSC mainly causes polarization of BMDM into M2 macrophages, and phenotypic transformation of glucose metabolism into high-energy and high-glycolytic metabolism, and affects inflammatory responses in BMDM.

Cone Beam Computed Tomography in observing the presence and location of canalis sinuosus.

OBJECTIVE: Cone Beam Computed Tomography (CBCT) was used to observe and describe the distribution of canalis sinuosus (CS) in the Chinese population and the location of CS in the maxillary alveolar bone, so as to help oral surgeons evaluate the intraoperative risk and prognosis before maxillary surgery and reduce the complications caused by the injury of this structure in anterior surgery. PATIENTS AND METHODS: CBCT images of 600 patients admitted from 2021 to 2022 were collected to observe the anatomical structure of CS in the maxillary region. The following parameters were recorded: age, sex, number of CS, left and right distribution of CS, CS diameter, and location. Statistical analysis was performed on all of the collected data. RESULTS: The discovery rate of CS in this study was 59.75%, and it is commonly found in the lateral incisor area (64.82%). No significant difference can be found in the presence and number of CS in different gender and age groups (p>0.05). CONCLUSIONS: The use of high-resolution CBCT before implantation is of irreplaceable significance in the diagnosis and analysis of CS, which is conducive to reducing implantation complications and failure rate. The incidence of CS was independent of age or sex, while the location of CS was statistically significant.

Multiparameter spectral CT-based radiomics in predicting the expression of programmed death ligand 1 in non-small-cell lung cancer.

AIM: To explore the value of radiomics for predicting the expression of programmed death ligand 1 (PD-L1) in non-small-cell lung cancer (NSCLC) based on multiparameter spectral computed tomography (CT) images. MATERIALS AND METHODS: A total of 220 patients with NSCLC were enrolled retrospectively and divided into the training (n=176) and testing (n=44) cohorts. The radiomics features were extracted from the conventional CT images, mono-energy 40 keV images, iodine density (ID) maps, Z-effective maps, and electron density maps. The logistic regression (LR) and support vector machine (SVM) algorithms were employed to build models based on radiomics signatures. The prediction abilities were qualified by the area under the curve (AUC) obtained from the receiver operating characteristic (ROC) curve. Internal validation was performed on the independent testing dataset. RESULTS: The combined model for PD-L1 ≥1%, which consisted of the radiomics score (rad-score; p<0.0001), white blood cell (WBC; p=0.027) counts, and air bronchogram (p=0.003), reached the highest performance with the AUCs of 0.873 and 0.917 in the training and testing dataset, respectively, which was better than the radiomics model with the AUCs of 0.842 and 0.886. The combined model for PD-L1 ≥50%, which consisted of rad-score (p<0.0001) and WBC counts (p=0.027), achieved the highest performance in the training and testing dataset with AUCs of 0.932 and 0.903, respectively, which was better than the radiomics model with AUCs of 0.920 and 0.892, respectively. CONCLUSION: The radiomics model based on the multiparameter images of spectral CT can predict the expression level of PD-L1 in NSCLC. The combined model can obtain higher prediction efficiency and serves as a promising method for immunotherapy selection.

The clinical applications of D-type parastomal hernia repair surgery.

OBJECTIVE: This study investigated the use of a modified laparoscopic repair of paraostomy hernia technique, called "D-Type parastomal hernia repair surgery" which combines abdominal wall and extraperitoneal stoma reconstruction, in patients with parastomal hernia (PSH) following colorectal stoma surgery. The aim was to determine whether D-type parastomal hernia repair surgery is a promising surgical approach compared to the traditional laparoscopic repair technique (Sugarbaker method) for patients with PSH. METHODS: PSH patients were selected and retrospectively divided into two groups: the study group underwent D-type parastomal hernia repair, while the control group underwent laparoscopic Sugarbaker repair. Clinical data from both groups were analyzed. RESULT: Compared to control group (n = 68), the study group undergoing D-type stoma lateral hernia repair had significant increase in total operative time (98.82 ± 12.37 min vs 124.61 ± 34.99 min, p < 0.001). The study group also showed better postoperative stoma bowel function scores in sensory ability, frequency of bowel movements, and clothing cleanliness without a stoma bag (p = 0.037, 0.001, 0.002). The treatment cost was significantly higher in the control group (3899.97 ± 260.00$ vs 3215.91 ± 230.03$, p < 0.001). The postoperative recurrence rate in the control group was 26.4%, while in the study group, it was 4.3%, with a significant statistical difference (p = 0.024). In terms of long-term postoperative complications, the study group had an overall lower incidence compared to the control group (p = 0.035). Other parameters showed no significant differences between the two groups. CONCLUSION: The study suggests that D-type parastomal hernia repair surgery is a safe and feasible procedure. Compared to traditional surgery, it can reduce the recurrence of lateral hernia, improve postoperative stoma bowel function, and save medical resources.

[Properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle Chlorella and its effects on healing of infected full-thickness skin defect wounds in mice].

Objective: To explore the properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle (AgNP) Chlorella (hereinafter referred to as the composite hydrogel) and its effects on healing of infected full-thickness skin defect wounds in mice. Methods: The research was an experimental research. The simple gelatin-polyethylene glycol hydrogel (hereinafter referred to as the simple hydrogel) and the composite hydrogel were prepared, and the appearance and injectability of the two hydrogels were observed at 55 and 37 ℃, and under the irradiation of 808 nm near-infrared light, respectively. An electronic universal testing machine was employed to assess the tensile and compressive stress-strain properties of both types of hydrogels at room temperature. Additionally, the cyclic compressive stress-strain properties of the composite hydrogel were examined at 80% of the maximum compressive stress. Staphylococcus aureus or Escherichia coli solution was added to phosphate buffer solution (PBS), simple hydrogel, and composite hydrogel, respectively. The part of composite hydrogel containing Staphylococcus aureus or Escherichia coli solution was irradiated with near-infrared light for 5 minutes. After each sample was incubated for 6 h, the dilution plating method was used to detect and calculate the mortality rates of the two bacteria at 24 h of culture (n=5). The discarded foreskin tissue was taken from a 6-year-old healthy boy admitted to the Department of Urology of the First Affiliated Hospital of Naval Medical University for circumcision. Primary human fibroblasts (HFbs) were isolated using the enzyme extraction method, routinely cultured to the 3rd to 6th passages for subsequent cellular experiments. Composite hydrogel extracts with final mass concentrations of 100.0, 50.0, 25.0, 12.5, and 0 mg/mL were respectively prepared and used to culture HFbs, and the cell proliferation after 24 h of culture was detected using a cell counting kit 8 (n=3). A total of twenty 6-8 weeks old C57BL/6J female mice were utilized, and a full-thickness skin defect was surgically created on the back of each mouse. The wounds were infected with Staphylococcus aureus solution. The infected mice were divided into blank control group, simple hydrogel group, composite hydrogel group, and combined treatment group according to the random number table, and the wounds were treated with PBS, simple hydrogel, composite hydrogel, and composite hydrogel+light irradiation (under the irradiation of 808 nm near-infrared light for 5 min), respectively, with 5 mice in each group. On post injury day (PID) 0 (immediately after the first wound treatment), 3, 7, and 14, an overall assessment of wound exudation and healing were conducted, and the wound healing rates on PID 7 and 14 were calculated (n=5). On PID 14, hematoxylin-eosin staining was performed to observe histopathological changes in the mouse wound. Results: Both simple hydrogel and composite hydrogel were in a solution state at 55 ℃ and transition to a gel state when cooling to 37 ℃. After the two hydrogels were irradiated by near-infrared light, only the composite hydrogel reheated up and returned to the solution state again with injectability. The maximum tensile stress of the composite hydrogel was up to 301.42 kPa, with a corresponding strain of 87.19%; the maximum compressive stress was up to 413.79 kPa, with a corresponding strain of 91.67%, which was similar to the tensile and compressive properties of the simple hydrogel. After 10 compression cycles, the maximum compressive stress of the composite hydrogel still reached 84.1% of the first compressive stress. After 24 h of culture, the mortality rate of Staphylococcus aureus treated with simple hydrogel was significantly higher than that treated with PBS (P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel alone were significantly higher than those treated with simple hydrogel (P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel+light irradiation were significantly higher than those treated with composite hydrogel alone (P<0.05). After 24 h of culture, compared with that cultured in composite hydrogel immersion solution with final mass concentration of 0 mg/mL, the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentrations of 25.0 and 50.0 mg/mL was significantly enhanced (P<0.05), while the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentration of 100 mg/mL was significantly decreased (P<0.05). On PID 0 and 3, more purulent secretions were seen in the wounds of mice in blank control group and simple hydrogel group, while only a small amount of exudate was observed in the wounds of mice in composite hydrogel group, and no obvious infection was observed in the wounds of mice in combined treatment group. On PID 7 and 14, the wound healing rates of mice in simple hydrogel group were significantly higher than those in blank control group (P<0.05); the wound healing rates of mice in composite hydrogel group were significantly higher than those in simple hydrogel group (P<0.05); the wound healing rates in combined treatment group were significantly higher than those in composite hydrogel group (P<0.05). On PID 14, the wounds of mice in blank control group exhibited a high infiltration of inflammatory cells with no new epithelial layer observed; the wounds of mice in simple hydrogel group displayed a short length of newly formed epithelium with a small amount of inflammatory cells; the wounds of mice in composite hydrogel group exhibited continuous formation of new epithelium and a large amount of immature granulation tissue; the wounds of mice in combined treatment group showed continuous epithelialization with less immature granulation tissue. Conclusions: The prepared composite hydrogel exhibits excellent thermosensitivity, photothermal properties, and injectability, as well as excellent mechanical properties, antibacterial properties, and biocompatibility, and can promote the healing of infected full-thickness skin defect wounds in mice.

[Effects of type 2 inflammation on bronchodilator responsiveness of large and small airways in chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the impact of type 2 inflammation markers blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO) on bronchodilator responsiveness (BDR) in patients with chronic obstructive pulmonary disease (COPD). METHODS: This study was conducted among 389 patients with an established diagnosis of COPD in our hospital from October, 2019 to October, 2023, who all underwent bronchial dilation test (BDT) of the large and small airways. Based on smoking history, blood EOS, and FeNO, these patients were divided group A (blood EOS < 300/µL + FeNO < 35 ppb + smoking history < 20 pack-years), group B (blood EOS < 300/µL+FeNO < 35 ppb+smoking history ≥20 pack-years), group C (blood EOS ≥300/µL or FeNO≥35 ppb+smoking history ≥20 pack-years), and group D (blood EOS ≥300/µL or FeNO ≥35 ppb+smoking history < 20 pack-years) for analyzing the relationship between clinical indexes and BDR. RESULTS: BDR evaluation based on forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) yielded consistent results, all showing a younger mean age, higher FeNO levels, and higher blood EOS counts and percentages in patients positive for BDT (P < 0.05). The improvement value and improvement rate of FEV1 were significantly lower in group A than in group D. The improvement value and improvement rate of FEV1 as well as the improvement rate of MMEF were significantly lower in group B than in group D. In the overall patients, age and FeNO were significantly correlated with the improvement value and improvement rate of FEV1 and the improvement rate of MMEF (P < 0.05). CONCLUSION: Type 2 inflammation markers have different effects on BDR in the large and small airways of COPD patients, and their clinical significance needs further investigation.

Lifestyle and Socioeconomic Transition and Health Consequences of Alzheimer's Disease and Other Dementias in Global, from 1990 to 2019.

BACKGROUND: Previous studies only focused on changes in the global age-specific incidence and mortality for Alzheimer's disease and other dementias, failed to distinguish between cohort and period effects, and did not discuss risk factors separately. METHODS: In this study, Alzheimer's disease disability-adjusted life years (DALYs) data to estimate the burden by gender, age, locations, and social-demographic status for 21 regions from 1990 to 2019. Additionally, trend analysis was performed using the age-period-cohort (APC) model and Join-point model. RESULTS: In most regions, indicators (incidence, mortality, and DALYs) increased steadily with socio-demographic index(SDI) increased. The age effects for Alzheimer's disease and other dementias showed a significant increase from 40 to 95 years. The cohort effects rate ratios (RRs) had a rapid reduction attributed to smoking, high fasting plasma glucose, and high body mass index (BMI). CONCLUSIONS: Countries in middle-low and low SDI regions have higher levels of risk factor exposure. As a result, rapid and effective government responses are necessary to control dementia risk factors and reduce the disease burden in these countries.

Ethical Reflection on the "QR code Dilemma" Faced by Older People During COVID-19 in China.

The widespread application of QR code technology is best represented by the health codes used in China's pandemic prevention and control. This technology has enhanced the country's ability to manage the pandemic by achieving higher efficiency and accuracy. Unfortunately, a certain segment of the older population has encountered difficulties in adapting and maintaining their daily activities. This indicates the limitations of QR code technology in achieving social isolation. This article argues that for a more comprehensive pandemic prevention and control policy system to be established, managing the implementation of this very technology should be done in a more humane fashion, i.e. under the guidance of three moral principles: benevolence, justice, and non-maleficence. By doing so, implementation of QR code technology is done in a way that is not only conducive to COVID-19 prevention and control but also mitigate marginalization of the older people. In the post-pandemic era, the socialization of digital technology will accelerate. Therefore, in the field of public health, we should direct attention not only to the fair distribution of resources but also to the issue of identity that arises due to digital divide.

[A three-dimensional imaging study of the effect of anterior disc displacement on the bony structural relationship of the temporomandibular joint].

Objective: To investigate the correlation between the osseous structure of temporomandibular joint (TMJ) and three different status of anterior disc location, so that it could guide the clinical diagnosis further. Methods: Fifty-two patients [46 females and 6 males, with an age of (27.8±8.3) years] who treated with MRI and cone beam CT, were recruited from the Temporomandibular Joint Specialist Clinic, The First Affiliated Hospital of Xinjiang Medical University, between March 2018 to December 2021. According to the radiographic findings of the level of anterior disc displacement (ADD) in TMJ, patients were divided into three groups: normal articular disc position (NADP, n=28 TMJs), anterior disc displacement with reduction (ADDWR, n=28 TMJs), and anterior disc displacement without reduction (ADDWoR, n=28 TMJs). In the light of the reconstructed three-dimensional model, ten representative morphological parameters including condylar volume (CV), condylar superficial area (CSA), fossa volume (FV), fossa superficial area (FSA), the proportion of the condylar volume in the articular fossa (CV%), the proportion of the condylar superficial area in the articular fossa (CSA%), superior joint space (SJS), anterior joint space (AJS), posterior joint space (PJS), and medial joint space (MJS), were measured respectively under one-way analysis of variance (ANOVA), Kruskal-Wallis Htest and receiver operator characteristic curve(ROC curve) analyses. Results: CV and CSA values varied significantly in the pathological progression from normal location to irreversible anterior displacement in TMJ. For CV value, NADP group [(1 834.90±667.67) mm3]>ADDWR group [(1 747.34±369.42) mm3]>ADDWoR group [(1 256.29±418.27) mm3] [t=4.31, P(NADP-ADDWoR)<0.001; t=3.66, P(ADDWR-ADDWoR)<0.001], for CSA value, NADP group [(859.27±216.01) mm2]>ADDWR group [(838.23±118.82) mm2]>ADDWoR group [(669.14±150.26) mm2] [t=4.27, P(NADP-ADDWoR)<0.001; t=3.80, P(ADDWR-ADDWoR)<0.001]. The difference of SJS value in NADP group [(2.22±0.88) mm], ADDWR group [(1.94±0.64) mm] and ADDWoR group [(1.45±0.57) mm], was statistically significant [t=4.11, P(NADP-ADDWoR)<0.001; t=2.63, P(ADDWR-ADDWoR)=0.010]. The results of MJS in NADP group [(5.03±1.41) mm], ADDWR group [(3.86±1.32) mm], and ADDWoR group [(4.91±1.65) mm] were significantly different [t=3.00, P(NADP-ADDWR)=0.004; t=2.63, P(ADDWR-ADDWoR)=0.009]. As calculated by the ROC curve analysis, CV, CSA and SJS showed that (AUCCV=0.77, AUCCSA=0.76; AUCSJS=0.76) for the NADP and ADDWoR groups, and (AUCCV=0.80; AUCCSA=0.80; AUCSJS=0.72) for the ADDWR and ADDWoR groups. While the diagnostic accuracy of MJS for the comparison in NADP versus ADDWR and ADDWR versus ADDWoR was respectively AUC(NADP-ADDWR)=0.73, and AUC(ADDWR-ADDWoR)=0.69. Conclusions: CV, CSA, SJS, and MJS were significantly associated with the different disc displacement status, and the condyle in TMJ ADD exhibited three-dimensionally altered dimensions. They could be considered as promising biometric markers to diagnose the ADD status.

[Research progress in clinical diagnosis and treatment of osteosarcoma of the jaw].

Osteosarcoma of the jaw (JOS), is a relatively rare type of osteosarcoma, with a unique pathogenesis and pathological manifestations. The clinical manifestation of JOS is not characteristic, and it often needs to be diagnosed by combining radiological and pathological examination. At present, the conventional treatment of JOS is a comprehensive treatment based on surgery and supplemented by radiotherapy and chemotherapy. Recently, the emergence of new therapies such as immunotherapy, gene therapy, phototherapy and traditional Chinese medicine has provided more choices for treatment and brought new hope to patients with JOS. Therefore, this article summarized the current understanding of diagnosis and the latest treatment development of JOS.

Preoperative diagnostic value of coronary CT angiography in acute Stanford type A aortic dissection involving the coronary arteries.

AIM: To assess the diagnostic value of coronary computed tomography angiography (CCTA) in acute type A aortic dissection (ATAAD) with coronary artery involvement and to evaluate whether CCTA could provide potentially useful information for selecting the surgical method. MATERIALS AND METHODS: Patients with ATAAD treated from January 2019 to December 2020 were reviewed retrospectively. Involvement of the coronary arteries based on CCTA findings were grouped into three major types and five subtypes. Interobserver and intraobserver diagnostic agreement for five subtypes were determined. The patients were divided into the coronary artery bypass grafting (CABG) and non-CABG groups, and the proportions of the five subtypes between the two groups were compared. RESULTS: A total of 95 patients were enrolled in this study. Interobserver and intraobserver diagnostic agreement were both substantial in the left and right coronary arteries. Overall, the proportions of the five subtypes of coronary artery involvement were significantly different between the two groups (p<0.001). The proportion of Type A was elevated in the non-CABG group compared with the CABG group (22.6% versus 71.9%); by contrast, the proportions of Type B1 (35.5% versus 14.1%), Type B2 (19.4% versus 10.9%), Type C1 (6.5% versus 0%), and Type C2 (16.1% versus 3.1%) were elevated in the CABG group. CONCLUSION: CCTA is reliable in evaluating coronary artery involvement by ATAAD. The present retrospective study indicated that CABG may be considered if the intimal flap disrupts the coronary orifice and causes luminal stenosis >50%, particularly Type B, or if an intimal tear occurs in the coronary orifice (Type C), which deserve further validation through prospective studies.

Feasibility study of the multishot gradient-echo planar imaging sequence in non-enhanced and free-breathing whole-heart magnetic resonance coronary angiography.

AIM: To investigate the feasibility of non-enhanced and free-breathing whole-heart magnetic resonance coronary angiography (MRCA) using multishot gradient-echo planar imaging (MSG-EPI). MATERIALS AND METHODS: In total, 29 healthy volunteers were recruited for free-breathing whole-heart MRCA acquisition using the MSG-EPI sequence and fast gradient echo (GRE) sequence. After the examination, the actual scanning times, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the left main (LM) coronary artery, subjective quality scores for each segment, and evaluable length of the coronary artery were recorded and statistically analysed. RESULTS: There was no significant difference between the SNRLM of the MSG-EPI sequence and fast GRE sequence (p=0.130), but the CNRLM of the MSG-EPI sequence was higher (p=0.001). The subjective quality score of the mid- and distal left anterior descending branch as well as the distal circumflex branch of the coronary artery in the MSG-EPI sequence was higher than that in the fast GRE sequence (p=0.003, 0.001, and 0.003, respectively). The evaluable length of the left anterior descending branch and the circumflex branch was better using the MSG-EPI sequence than that of the fast GRE sequence (p=0.015 and < 0.001, respectively). Moreover, the scanning time of the MSG-EPI sequence was 54.5% less than that of the fast GRE sequence (p<0.001). CONCLUSION: The MSG-EPI sequence improves the subjective and objective image quality of MRCA as well as reduces the scanning time.

Distinguishment between high-grade gliomas and solitary brain metastases in peritumoural oedema: quantitative analysis using synthetic MRI at 3 T.

AIM: To investigate the efficacy of synthetic magnetic resonance imaging (MRI) in distinguishing high-grade gliomas (HGGs) from solitary brain metastases (SBMs) in peritumoural oedema. MATERIALS AND METHODS: Thirty-five patients with HGGs and 25 patients with SBMs were recruited and scanned using synthetic MRI using a 3 T scanner. Two radiologists measured synthetic MRI-derived relaxation values independently (T1, T2, proton density [PD]) in the peritumoural oedema, which was used to generate quantitative metrics before (T1native, T2native, and PDnative) and after (T1post, T2post, and PDpost) contrast agent injection. Student's t-test or the Mann-Whitney U-test was performed to detect statistically significant differences in the aforementioned metrics in peritumoural oedema between HGGs and SBMs. The receiver operating characteristic (ROC) curves were plotted to evaluate the efficacy of each metric in distinguishing the two groups, and the areas under the curves (AUCs) were compared pairwise by performing the Delong test. RESULTS: The mean T1native, T2native, and T1post values in the peritumoural oedema of HGGs were significantly lower compared with SBMs (all p<0.05). The T1post value had a higher AUC (0.843) in differentiating HGGs and SBMs than all other individual metrics (all p<0.05). The combined T1native, T2native, and T1post model had the best distinguishing performance with an AUC, sensitivity, and specificity of 0.987, 94.3%, and 100%, respectively. CONCLUSIONS: Synthetic MRI may be a potential supplement to the preoperative diagnosis of HGGs and SBMs in clinical practice, as the synthetic MRI-derived tri-parametric model in the peritumoural oedema showed significantly improved diagnostic performance in distinguishing HGGs from SBMs.

[Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone].

Objective: To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods: A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses. Results: A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) (χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months (χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS (χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group (χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy (HR=0.11, 95%CI 0.05-0.27), achievement of efficacy of partial response or better (HR=0.47, 95%CI 0.34-0.66), and non-aggressive relapse (HR=0.25, 95%CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion: In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

[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.