Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia， recurrent joint swelling and pain， and tophus formation. The disease course is divided into three stages： The hyperuricemia stage， acute attack stage， and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology， but traditional Chinese medicine （TCM） lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms， making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory， clinical practice， and modern medical understanding， and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber， our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities， it manifests as ''spleen deficiency with impaired transport and transformation''， resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels， serum uric acid levels rise. When it stagnates in the viscera and limbs， monosodium urate crystals deposit in the joints. Triggered by precipitating factors， this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory， the stage-specific pathogenic characteristics of gout are proposed： The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation， internal retention of pathogenic dampness-turbidity''， the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints''， while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity， intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage， treatment focuses on ''strengthening the spleen， draining dampness， and eliminating turbidity''. In the acute attack stage， the treatment should "strengthen the spleen， drain dampness， clear heat， eliminate turbidity， alleviate swelling， and relieve pain''. In the chronic stage， the treatments emphasizes to ''strengthen the spleen， drain dampness， transform turbidity， clear heat， resolve phlegm， and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root， dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research， providing systematic theoretical guidance and a practical framework for the precise TCM management of gout， thereby promoting the modernization of TCM pathogenesis theory related to gout.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

Purpose: Lung cancer is frequently observed as a second primary malignancy following gastric cancer, yet the genetic causality between them remains uncertain. This study aims to evaluate the causal relationship between gastric and lung cancers using Mendelian randomization (MR) analysis. Materials and Methods: Single nucleotide polymorphisms associated with gastric and lung cancers were selected from genome-wide association study in East Asian and European populations as instrumental variables. The causal effects between gastric and lung cancers were evaluated using univariable and multivariable MR analysis, with the inverse variance weighted (IVW) method serving as the primary criterion. Heterogeneity and sensitivity analyses were performed to ensure the robustness of the findings. Results: Univariable MR analysis demonstrated that genetic susceptibility to gastric cancer in the European population was significantly associated with an increased risk of lung cancer (IVW: odds ratio [OR], 1.285; 95% confidence interval [CI], 1.072 to 1.541; p=6.83E-03), which was consistently validated in the East Asian population (IVW: OR, 1.356; 95% CI, 1.114 to 1.651; p=2.40E-03). Multivariable MR analysis further indicated that the significant positive causal relationship between gastric cancer and lung cancer persisted in both populations after adjusting for confounding factors (all p < 0.05). Conversely, no significant causal relationship was observed for the risk of developing gastric cancer following the diagnosis of lung cancer in either population (p > 0.05). Conclusion This study confirms that genetic susceptibility to gastric cancer increases the risk of lung cancer. This finding provides a theoretical basis for exploring the underlying biological mechanisms and suggests that enhancing lung cancer screening in patients with gastric cancer may be necessary to improve patient prognosis.

Hereditary carotid body tumor (HCBT) is a rare neuroendocrine tumor mainly caused by germline mutations of the SDHx gene. Its multifocality, familial aggregation, and potential malignant risk pose unique challenges to diagnosis and treatment. This review systematically expounds the molecular mechanism of HCBT, pointing out that SDHx mutations drive tumorigenesis through the “pseudo-hypoxia” pathway and are regulated by epigenetic and somatic mutations. In terms of diagnosis, we emphasize the crucial role of ⁶⁸Ga-DOTATATE PET/CT and SDHB immunohistochemistry and advocate for multigene panel sequencing for patients with high-risk characteristics (such as early-onset, multifocal, family history or malignant signs) to clarify the genetic background. On the basis of existing evidence, we recommend conducting baseline biochemical tests for all newly diagnosed patients and actively suggest genetic screening for high-risk individuals such as those who are young, have multifocal tumors, or have a family history. In terms of treatment, surgery is the main treatment method for HCBT. Nevertheless, individualized strategies still need to be formulated based on tumor classification and patient’s overall condition and genetic background. Comprehensive management measures such as targeted therapy, radionuclide therapy, and standardized family management are crucial for improving the prognosis of patients.

Objective To investigate the diagnosis and treatment of 2 cases with spontaneous renal vascular rupture, and discuss the possible causes and treatment methods of this disease. Methods The clinical data and treatment methods of the 2 patients with spontaneous renal vascular rupture treated with renal artery embolization in Universal Global Xi'an Beihuan Hospital were analyzed. Relevant literature was reviewed to summarize the possible causes of this condition. Results The patients had no obvious history of trauma and no obvious abnormal coagulation function, and sought treatment due to sudden lumbar and abdominal pain. Laboratory tests revealed significantly decreased hemoglobin level, and elevated blood glucose (27.8, 27.6mmol/L). Abdominal computed tomography (CT) indicated perirenal hematoma and active bleeding. The bleeding arteries were located at the terminal branches of the anterior renal artery. Precise embolization was performed using CT angiography and selective renal artery angiography plus embolization, achieving an immediate hemostasis success rate of 100%. Postoperative hemoglobin level stabilized, and follow-up CT scans showed significant absorption of the perirenal hematoma without significant deterioration of renal function. Based on literature review and case analysis, the possible cause of spontaneous renal vascular rupture in these two patients was renal vascular sclerosis due to long-term diabetes. Other common etiologies of this condition included renal tumor, vascular malformation, and hypertension. Conclusion Spontaneous renal vascular rupture is rare. Renal artery embolization, as aminimally invasive treatment, can effectively control bleeding and protect renal function. The specific pathogenesis of this condition still requires further investigation. Long-term diabetes mellitus with poor blood glucose control may be associated factors, but more evidence is needed.

ObjectiveTo analyze the changing trend of the disease burden of acute viral hepatitis （AVH） globally and in China from 1990 to 2021， and to provide a basis for optimizing prevention and control strategies. MethodsRelated data were extracted from the Global Burden of Disease 2021 database， including incidence rate， mortality rate， and disability-adjusted life years （DALY） for AVH globally and in China from 1990 to 2021， and the patients were divided into groups according to region， age， sex， and type of hepatitis. The Joinpoint regression model was used to calculate average annual percentage change （AAPC） and its 95% confidence interval （CI）. ResultsFrom 1990 to 2021， there was a tendency of reduction in the age-standardized incidence rate， mortality rate， and DALY rate of AVH globally， with an average annual reduction of 1.02% （95%CI： -1.10% to -0.94%， P<0.001）， 3.97% （95%CI： -4.12% to -3.82%， P<0.001）， and 3.64% （95%CI： -3.84% to -3.44%， P<0.001）， respectively； in China， there was also a tendency of reduction in these indicators， with an average annual reduction of 1.63% （95%CI： -1.70% to -1.57%， P<0.001）， 9.24% （95%CI： -9.51% to -8.97%， P<0.001）， and 7.93% （95%CI： -8.15% to -7.71%， P<0.001）， respectively. In addition， China’s share of the global disease burden of AVH continued to decrease； the proportion of new cases decreased from 24% in 1990 to 15% in 2021， the proportion of deaths decreased from 19% to 4%， and the proportion of DALY decreased from 16% to 4%. From 1990 to 2021 globally， the peaks in the incidence rate， mortality， and DALY of AVH were observed in children under 5 years of age； in China， although the peak incidence rate of the disease was still observed in children under 5 years of age， there was a tendency of increase in the incidence rate of AVH among young adults aged 25 — 29 years in recent years， with the most significant increase in the cases of acute hepatitis B （accounting for 59% of the cases in this age group）， while the disease burden of mortality and DALY mainly affected the middle-aged and elderly populations. The disease burden of AVH in the male population was higher than that in the female population. As for the distribution of disease types， acute hepatitis A was the predominant type of AVH， accounting for 64% globally and 48% in China， whereas acute hepatitis B was the leading cause of mortality and DALY， accounting for 50% of deaths globally， 80% of deaths in China， 47% of DALY globally， and 69% of DALY in China. ConclusionThere is a tendency of reduction in the disease burden of AVH globally and in China from 1990 to 2021， but there is a tendency of increase in the incidence rate of AVH among young adults in China， especially acute hepatitis B. It is necessary to implement targeted prevention and control strategies.

Objective: To explore the association between various components of sleep quality and the co-occurrence of non-suicidal self-injury (NSSI) behaviors and depressive symptoms among junior high school students, so as to provide evidence for targeted prevention strategies of NSSI and depression. Methods: From May to June 2024, a total of 5 008 junior high school students from 8 schools in 2 districts/counties of Chongqing were selected through a stratified cluster sampling method. The Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiological Studies Depression Scale (CES-D), and the Adolescent Non suicidal Self injury Assessment Questionnaire (ANSAQ) were used to assess sleep quality, depressive symptoms, and NSSI, respectively. Data were analyzed by using the Chi-square test, Bonferroni correction, and multivariate Logistic regression. Results: Non-NSSI group and depressive symptoms group accounted for 68.11% among junior high school students, NSSI-only group accounted for 4.71%, only depressive symptoms group accounted for 14.94%, and co-occurrence of NSSI and depressive symptoms group accounted for 12.24%. The prevalence of the co-occurrence group was higher in girls (16.39%) than in boys (7.85%) ( χ 2=84.89, P <0.01). After controlling for gender, grade, and boarding status etc., multivariate Logistic regression analysis revealed that five sleep components, including subjective sleep quality, sleep latency, sleep duration, sleep disturbances, and daytime dysfunction, were significantly and positively associated with the co-occurrence of NSSI and depressive symptoms ( OR =1.30-3.86, all P <0.05). The strength of association between these components and the co-occurrence group, in descending order, was: daytime dysfunction ( OR = 2.52), sleep disturbances ( OR =2.36), subjective sleep quality ( OR =1.76), sleep latency ( OR =1.44), and sleep duration ( OR =1.22) (all P <0.01). Conclusions The co-occurrence of NSSI and depressive symptoms is prevalent among junior high school students, with girls being more significantly affected. Sleep disturbances and daytime dysfunction may represent particularly important risk factors. Targeted and prioritized intervention strategies addressing specific sleep components should be developed and implemented to reduce the co-occurrence of NSSI and depressive symptoms in junior high school students.

Objective:To establish an element framework and template of broad informed consent applicable to clinical research,and to standardize the collection,storage,and reuse of medical data and biological samples,making them comply with ethical and legal requirements.Methods:A literature review and group discussion were employed to construct the draft of the element framework and template of broad informed consent form.The Delphi expert consultation method was used to conduct two rounds of correspondence with 13 experts in relevant fields to determine the two-level element framework and template of broad informed consent form.Results:The response rates for the two rounds of expert consultation questionnaires were above 90%,the experts'positive coefficients were good,and the coefficients of authority(Cr)were higher than 0.85.In the second round of consultation,the average importance value was≥4.4,the coefficient of variation(CV)was<0.17,and Kendall's W was 0.184(P<0.001),indicating that the expert opinions tended to be consistent.Ultimately,an element framework and template of broad informed consent form was established,consisting of 4 first-level items and 21 second-level items.Conclusion:The constructed element framework and template of broad informed consent form is highly scientific and applicable,providing references for clinical research.

Objective:To investigate the prevalence and genotype distribution of human papillomavirus (HPV) infection in the anorectal region among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) in Shenzhen, and explore the differences between HIV-positive and HIV-negative MSM populations, providing scientific evidence for HPV screening, vaccination, and related disease prevention.Methods:A total of 100 MSM recruited from the Department of Dermatovenerology of the Third People′s Hospital of Shenzhen between 2023 and 2024 were included. Questionnaire collected sociodemographic and clinical characteristics. Anorectal exfoliated cells were analyzed for HPV genotyping, and blood samples were tested for HIV antibodies and T lymphocyte subsets. Chi-square test was used to assess associations between qualitative variables. Results:Among 100 MSM, 58 were HIV-positive and 42 HIV-negative. The overall HPV infection rate was 93.10% (54/58) in HIV-positive MSM, with high-risk HPV at 79.31% (46/58) and low-risk HPV at 75.86% (44/58). The predominant genotypes were HPV6, 11, 16, 52, 18, 59, and 68. In HIV-negative MSM, HPV infection rate was 95.24% (40/42), with high-risk HPV at 57.14% (24/42) and low-risk HPV at 92.50% (37/40), dominated by HPV6, 11, 16, 51 and 52. HIV-positive MSM showed significantly higher infection rates of high-risk HPV16/18 ( P=0.032), HPV58 ( P=0.020), HPV59 ( P=0.031), and HPV68 ( P=0.007) compared to HIV-negative MSM. The maximum number of concurrent HPV infections was 12 in HIV-positive MSM versus 4 in HIV-negative MSM. Multivariate analysis revealed that HIV-positive MSM with CD4/CD8 ratio≤0.9 had significantly higher HPV positivity ( P<0.05). Conclusions:HIV-positive MSM exhibit elevated rates of high-risk and multiple HPV infections, closely associated with immune dysfunction. Strengthened HPV screening, vaccination, and immune status management are critical for preventing HPV-related malignancies in the population.

Objective:To evaluate the prognosis of Hall technique and traditional performed metal crown (PMC) restoration technique, and to follow up the occlusal changes before and after treatment with Hall technique, providing references for the promotion of Hall technique.Methods:Children who visited the Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University from May 2021 to December 2022 were screened according to the inclusion and exclusion criteria. The therapeutic effects of the two groups were followed up at three time points: 1, 2 and 3 months after operation. The observation results were divided into three outcomes: success (crown in place, no symptoms of pulpitis or periapical periodontitis, no obvious abnormality in occlusion, no need for further treatment), partial failure (crown falling off or crown broken, tooth defect can be repaired, reversible pulpitis) and complete failure (irreversible pulpitis or periapical periodontitis, crown falling off and tooth defect irreparable), and statistical analysis was made. At the same time, the Hall technique group was followed up at five time points as before operation, immediately after operation, 2 weeks after operation, 4 weeks after operation and 8 weeks after operation respectively, in which the occlusion was analyzed by Dental Prescale Ⅱ system. The vertical dimension of occlusion (VDO), overbite and coverage, and canine relationship were recorded and compared. Three-dimensional finite element method was used to model and analyze the stress of the teeth treated with traditional PMC treatment and Hall technique, and the differences between them were compared.Results:Finally, 21 children were included in the Hall technique group, including 12 boys and 9 girls, with age of (5.0±1.4) years. Meanwhile, 22 children including 15 boys and 7 girls were in the traditional PMC group, with age of (5.1±1.3) years. There were 0 cases of complete failure and 0 cases of partial failure both in the Hall technique group and in the traditional PMC group within 1 month. There were 0 cases of complete failure and 1 case of partial failure in the Hall technique group, while 0 cases of complete failure and 0 cases of partial failure in the traditional PMC group within 2 months after operation. Hall technique group failed completely in 1 case and partially in 1 case, while the traditional pre-crown group failed completely in 0 cases and partially in 0 cases 3 months after operation. There was no significant difference in the incidence of primary index/complete failure and secondary index/partial failure between Hall technique group and traditional PMC group (all P>0.05). The occlusal area and occlusal force of children treated with Hall technique decreased immediately after operation compared with those before operation, but gradually recovered to the preoperative level at 2, 4 and 8 weeks after operation. To elaborate, the occlusal area decreased significantly from (14.79±3.55) mm 2 before operation to (10.15±3.17) mm 2 immediately after operation ( P=0.001), and recovered to (15.58±3.39) mm 2 at 8 weeks after operation ( P>0.05 compared with pre-operation). The occlusal force decreased significantly from (436.94±109.59) N before operation to (292.70±96.05) N immediately after operation ( P=0.001), and recovered to (441.86±104.31) N at 8 weeks after operation ( P>0.05 compared with pre-operation). Overbite decreased significantly from (2.54±1.05) mm before operation to (1.80±0.94) mm immediately after operation ( P=0.044) and then recovered to (2.35±1.02) mm ( P>0.05 compared with pre-operation). The coverage changed from (2.41±0.66) mm before operation to (2.27±0.61) mm immediately after operation ( P>0.05) and then recovered to (2.48±0.62) mm ( P>0.05 compared with pre-operation). The canine relationship was (3.12±0.54) mm before operation, and decreased significantly immediately after operation (2.17±0.89) mm ( P=0.001), and recovered to (3.05±0.61) mm after 8 weeks ( P>0.05 compared with pre-operation). In the three-dimensional finite element analysis, the maximum stress of all parts of the affected tooth increased immediately after Hall technique treatment, but with occlusal adjustment, the maximum stress of all parts of the affected tooth decreased, which was similar to that of the traditional metal pre-crown group. The vertical load and oblique load of pre-crown decreased from 180.11 and 496.16 MPa to 108.05 and 297.69 MPa, respectively. The vertical load and oblique load of enamel decreased from 94.83 and 255.94 MPa to 57.21 and 156.44 MPa, respectively. The vertical load and oblique load of dentin decreased from 55.19 and 124.77 MPa to 33.19 and 74.59 MPa, respectively. Conclusions:During the experimental observation period, there is no obvious difference between Hall technique and traditional PMC treatment technology in terms of post-treatment occlusion and clinical prognosis, which supports clinical application.