1.Analysis of Chronic Gouty Arthritis Animal Models Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Yan XIAO ; Siyuan LIN ; Fan YANG ; Qianglong CHEN ; Xiaohua CHEN ; Meiling WANG ; Zhen ZHANG ; Jiali LUO ; Youxin SU ; Jiemei GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):84-92
ObjectiveBased on the clinical characteristics of chronic gouty arthritis (CGA) in both traditional Chinese and western medicine, this study aims to systematically evaluate the clinical concordance of existing CGA animal models, providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure, Wanfang, VIP Chinese Science and Technology Periodical Database (VIP), and PubMed, all relevant literature on CGA animal models was collected. Based on the guidelines, the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes, and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction, high-protein diet induction (poultry lack urate oxidase), and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature, the traditional Chinese and western medicine scoring data of each model were extracted, and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%, respectively. Among them, the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection, achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA, they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore, in the future, it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria, providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.
2.Mechanism of Huazhuo Sanjie Chubi Presciption in Regulating Macrophage Polarization and Improving Low-grade Inflammation in Rats with Chronic Gouty Arthritis
Yuwan LI ; Yingjie ZHANG ; Siyuan LIN ; Xiaohua CHEN ; Qianglong CHEN ; Fan YANG ; Jun LIU ; Bingyan CHEN ; Peng CHEN ; Jiemei GUO ; Youxin SU ; Yan XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):93-104
ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption (HSCD) on chronic gouty arthritis (CGA) rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated, using the random number table, to a normal group (n=8) and a model group (n =33). CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate (250 mg·kg-1·d-1) and hypoxanthine (300 mg·kg-1·d-1), combined with intra-articular injection of a monosodium urate (MSU) crystal suspension (50 μL, 25 g·L-¹) into the left ankle twice weekly. After 4 weeks of modeling, 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group, an HSCD group (10.35 g·kg-1·d-1, gavage once daily), an M1 polarization agonist group (L-methionine sulfoximine, 300 mg·kg-1, subcutaneous injection every other day), an M1 polarization agonist + HSCD group, an M2 polarization inhibitor group (PD0325901, 10 mg·kg-1·d-1, gavage once daily), and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment, whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium (CMC-Na) vehicle (10.35 g·kg-1·d-1, gavage once daily). All interventions were continued for four weeks. During the intervention period, except for the normal group, potassium oxonate (250 mg·kg⁻¹) and hypoxanthine (300 mg·kg-1) were co-administered by gavage every other day to maintain the model. At the end of treatment, serum uric acid (SUA), ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), chemokine C-C motif ligand 2 (CCL2), S100 calcium-binding protein A8/A9 (S100A8/A9), interleukin-10 (IL-10) and arginase-1 (Arg-1) in serum and joint fluid were determined by enzyme-linked immunosorbent assay (ELISA). High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin (HE) staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase (iNOS) and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 (CD163) in synovial tissue. ResultsCompared with the normal group, the model group showed significantly elevated SUA level and joint swelling index, and increased levels of pro-inflammatory cytokines, CCL2, and S100A8/A9 in both serum and joint fluid (P<0.05), accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated (P<0.05). Compared with model group, rats in HSCD group had significantly lower SUA levels, attenuated joint swelling, reduced serum levels of pro-inflammatory cytokines, and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid, accompanied with alleviated MSU deposition and synovial inflammation (P<0.05). HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS (P<0.05), whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group, the M1 polarization agonist + HSCD group showed significantly reduced joint swelling, lower serum levels of pro-inflammatory cytokines, and decreased levels of CCL2 and S100A8/A9 in joint fluid (P<0.05). In addition, synovial inflammatory cell infiltration and angiogenesis were attenuated, and iNOS mRNA and protein expression levels were significantly reduced (P<0.05). Compared with the M2 polarization inhibitor group, the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling, decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation (P<0.05), whereas the levels of anti-inflammatory mediators (IL-10, Arg-1) and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats, at least in part, by inhibiting macrophage polarization toward the M1 phenotype.
3.Simultaneous TAVI and McKeown for esophageal cancer with severe aortic regurgitation: A case report
Liang CHENG ; Lulu LIU ; Xin XIAO ; Lin LIN ; Mei YANG ; Jingxiu FAN ; Hai YU ; Longqi CHEN ; Yingqiang GUO ; Yong YUAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):277-280
A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.
4.Analysis of distortion product otoacoustic emissions results of noise-exposed workers at a metal shipbuilding enterprise
Jieting ZHOU ; Jianyu GUO ; Hairu YANG ; Linyan SHU ; Zhixing FAN ; Jia TANG ; Xinqiang NIE ; Guoyong XU ; Hansheng LIN ; Bin XIAO
China Occupational Medicine 2025;52(1):99-105
Objective To evaluate the role of distortion product otoacoustic emissions (DPOAE) testing in evaluating early hearing loss among noise-exposed workers. Methods A total of 174 noise-exposed workers in a metal shipbuilding enterprise were selected as the research subjects by the convenience sampling method. Pure tone audiometry (PTA), DPOAE and the level of noise exposure were conducted on the workers. The rank correlation analysis was used to analyze the correlation between DPOAE amplitude and PTA threshold. The multilevel model was used to analyze the effects of gender, age, noise exposure intensity, cumulative noise exposure (CNE), hearing loss classification and PTA threshold on DPOAE results. Results At the frequencies of 0.50, 1.00, 2.00, 3.00, 4.00, 6.00 and 8.00 kHz, the DPOAE amplitude was negatively correlated with the PTA threshold (rank correlation coefficients were -0.12, -0.48, -0.47, -0.18, -0.23, -0.44, -0.19, respectively, all P<0.01). At the most frequencies, DPOAE amplitude was negatively correlated with age and CNE (all P<0.05). The results of multilevel model analysis showed that there were significant differences in DPOAE amplitudes at certain frequencies across gender, age, noise intensity, CNE, and hearing loss classification (all P<0.05). Significant differences in DPOAE responses were found among different CNE and hearing loss groups (all P<0.01). Conclusion DPOAE testing can objectively reflect the hearing status of noise-exposed workers and could be considered for inclusion in routine hearing monitoring to facilitate early detection of noise-induced hearing loss.
5.Scientific connotation of "blood stasis toxin" in hypoxic microenvironment: its "soil" function in tumor progression and micro-level treatment approaches.
Wei FAN ; Yuan-Lin LYU ; Xiao-Chen NI ; Kai-Yuan ZHANG ; Chu-Hang WANG ; Jia-Ning GUO ; Guang-Ji ZHANG ; Jian-Bo HUANG ; Tao JIANG
China Journal of Chinese Materia Medica 2025;50(12):3483-3488
The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans
;
Tumor Microenvironment/drug effects*
;
Neoplasms/therapy*
;
Animals
;
Medicine, Chinese Traditional
;
Disease Progression
;
Drugs, Chinese Herbal
6.Investigating the correlation between white matter injury and cerebral perfusion in preterm infants using arterial spin labeling.
Xiang-Bo KONG ; Fan-Yue QIN ; Wen-Li DUAN ; Lin LU ; Xiao-Chan GUO ; Yan-Ran XUE ; Yin-Gang HONG ; Fa-Lin XU
Chinese Journal of Contemporary Pediatrics 2025;27(6):661-667
OBJECTIVES:
To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL).
METHODS:
A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated.
RESULTS:
The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05).
CONCLUSIONS
WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans
;
White Matter/blood supply*
;
Infant, Newborn
;
Spin Labels
;
Infant, Premature
;
Female
;
Male
;
Cerebrovascular Circulation
;
Magnetic Resonance Imaging
7.Clinical and Laboratory Characteristics of Streptococcus mitis Causing Bloodstream Infection in Children with Hematological Disease.
Yu-Long FAN ; Guo-Qing ZHU ; Zhi-Ying TIAN ; Yan-Xia LYU ; Zhao WANG ; Ye GUO ; Wen-Yu YANG ; Qing-Song LIN ; Xiao-Juan CHEN
Journal of Experimental Hematology 2025;33(1):286-291
OBJECTIVE:
To investigate the risk factors, clinical characteristics, and bacterial resistance of bloodstream infections caused by Streptococcus mitis in children with hematological disease, so as to provide a reference for infection control.
METHODS:
The clinical information and laboratory findings of pediatric patients complicated with blood cultures positive for Streptococcus mitis from January 2018 to December 2020 in the Institute of Hematology & Blood Diseases Hospital were searched and collected. The clinical characteristics, susceptibility factors, and antibiotic resistance of the children were retrospectively analyzed.
RESULTS:
Data analysis from 2018 to 2020 showed that the proportion of Streptococcus mitis isolated from bloodstream infections in children (≤14 years old) with hematological diseases was the highest (19.91%) and significantly higher than other bacteria, accounting for 38.64% of Gram-positive cocci, and presented as an increasing trend year by year. A total of 427 children tested positive blood cultures, including 85 children with bloodstream infections caused by Streptococcus mitis who tested after fever. Most children experienced a recurrent high fever in the early and middle stages (≤6 d) of neutropenia and persistent fever for more than 3 days. After adjusting the antibiotics according to the preliminary drug susceptibility results, the body temperature of most children (63.5%) returned to normal within 4 days. The 85 children were mainly diagnosed with acute myeloid leukemia (AML), accounting for 84.7%. The proportion of children in the neutropenia stage was 97.7%. The incidence of oral mucosal damage, lung infection, and gastrointestinal injury symptoms was 40%, 31.8%, and 27.1%, respectively. The ratio of elevated C-reactive protein (CRP) and procalcitonin was 65.9% and 9.4%, respectively. All isolated strains of Streptococcus mitis were not resistant to vancomycin and linezolid, and the resistance rate to penicillin, cefotaxime, levofloxacin, and quinupristin-dalfopristin was 10.6%, 8.2%, 9.4%, and 14.1%, respectively. None of children died due to bloodstream infection caused by Streptococcus mitis.
CONCLUSION
The infection rate of Streptococcus mitis is increasing year by year in children with hematological diseases, especially in children with AML. Among them, neutropenia and oral mucosal damage after chemotherapy are high-risk infection factors. The common clinical symptoms include persistent high fever, oral mucosal damage, and elevated CRP. Penicillin and cephalosporins have good sensitivity. Linezolid, as a highly sensitive antibiotic, can effectively control infection and shorten the course of disease.
Humans
;
Child
;
Streptococcal Infections/microbiology*
;
Retrospective Studies
;
Hematologic Diseases/complications*
;
Streptococcus mitis
;
Drug Resistance, Bacterial
;
Risk Factors
;
Microbial Sensitivity Tests
;
Anti-Bacterial Agents
;
Female
;
Male
;
Bacteremia/microbiology*
;
Child, Preschool
;
Adolescent
8.Clinical Characteristics and Prognosis of Patients with IgD Multiple Myeloma.
Yong-Qian ZHANG ; Ji-Sheng ZHAO ; Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Qiao-Lin CHEN ; Qi-Ke ZHANG
Journal of Experimental Hematology 2025;33(2):437-441
OBJECTIVE:
To investigate the clinical characteristics and prognosis of patients with IgD multiple myeloma (MM).
METHODS:
The clinical data of 8 patients with IgD MM admitted to Gansu Provincial Hospital from September 2013 to February 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized.
RESULTS:
Among the 8 enrolled patients, there were 4 males and 4 females, with a median age of 60 (44-74) years. All patients had symptoms of renal insufficiency and anemia. There were 3 cases of bone invasion, 3 cases of splenomegaly, 7 cases of IgD-λ type, and 1 case of IgD-κ type. FISH examination was performed in 7 cases, and 6 of them were positive for 1q21 . There were 6 cases in DS stage III and 2 cases in DS stage II; According to ISS staging, there were 6 cases in stage III, 1 case in stage II, and 1 case in stage I; According to R-ISS staging, there were 5 cases in stage III and 3 cases in stage II. All patients received bortezomib-based combination chemotherapy, with 1 case undergoing autologous stem cell transplantation (ASCT) and 2 cases receiving daratumumab in combination. The median treatment period was 6 (1-15) cycles. The short-term efficacy was evaluated after 4-6 courses of treatment. Among the 6 patients with assessable efficacy, 1 case experienced disease progression (PD), and 5 cases achieved complete remission (CR). The median follow-up time was 26 (11-33) months, and the median progression-free survival (PFS) and median overall survival (OS) of the patients were 11.25 (3-26) months and 18.5 (4-33) months, respectively. Among the 8 patients, 4 cases died. Among the deceased patients, 3 cases were in R-ISS stage III and 3 cases were 1q21 positive. 2 of the 5 patients with early CR died due to disease progression.
CONCLUSION
The incidence of IgD MM is low, the symptoms of early renal damage, blood system damage and bone erosion in IgD MM patients are obvious, and the median survival time is short. ASCT and / or daratumumab may bring lasting relief for IgD MM patients, but large-scale clinical studies are still needed.
Humans
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Multiple Myeloma/therapy*
;
Middle Aged
;
Male
;
Female
;
Aged
;
Prognosis
;
Immunoglobulin D
;
Adult
;
Retrospective Studies
9.The Significance of Bone Marrow Plasma Cell Percentage and Immature Plasma Cells in the Prognosis of Newly Diagnosed Multiple Myeloma Patients.
Yuan-Yuan ZHANG ; Qi-Ke ZHANG ; Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Fei LIU ; Qiao-Lin CHEN ; Yang-Yang ZHAO ; Xiu-Juan HUANG ; Yang CHEN
Journal of Experimental Hematology 2025;33(2):469-474
OBJECTIVE:
To explore the significance of the plasma cell percentage and immature plasma cells in the prognosis of patients with multiple myeloma (MM).
METHODS:
The clinical data of 126 newly diagnosed MM patients in Gansu Provincial Hospital from June 2017 to November 2022 were retrospectively analyzed. The enrolled patients were divided into a higher plasma cell percentage group (group A) and a lower plasma cell percentage group (group B) according to the median plasma cell percentage (33.5%). The clinicopathological data of the two groups were compared, and the effect of plasma cell percentage on the prognosis of MM patients was analyzed using survival curves. On this basis, group A and group B were divided into subgroups with immature plasma cells (A1 group, B1 group) and subgroups without immature plasma cells (A2 group, B2 group), respectively, then the survival curves were used to analyze the effect of immature plasma cells on the prognosis of MM patients.
RESULTS:
Among the 126 patients with MM, the proportions of patients with ISS stage III, elevated β2-microglobulin(β2-MG) level, and immature plasma cells in Group A were significantly higher compared those in Group B ( P =0.015, P =0.028, P =0.010). The median overall survival(OS) and progression-free survival(PFS) of group A were 32 months and 10 months, respectively. The median OS of group B was not reached, and the median PFS was 32 months. The 3-year OS rates of patients in group A and group B were 46.7% and 62.2%, respectively ( P =0.021), and the 3-year PFS were 29.2% and 42.5%, respectively ( P =0.033). There were no significant differences in OS and PFS between group A1 and group A2, or between group B1 and group B2 ( P >0.05). Multivariate COX survival analysis showed that the plasma cell percentage ≥33.5%(HR=1.253, 95%CI : 0.580-2.889, P =0.018), age ≥65 years (HR=2.206, 95%CI : 1.170-3.510, P =0.012), lactate dehydrogenase(LDH) ≥250 U/L (HR=1.180, 95%CI : 0.621-2.398, P =0.048) and β2-MG ≥3.5 mg/L (HR=1.507, 95%CI : 0.823-3.657, P =0.036) were independent risk factors affecting OS in MM patients.
CONCLUSION
MM patients with a higher plasma cell percentage (≥33.5%) at the initial diagnosis have a later disease stage, poorer OS and PFS, compared to the patients with a lower percentage(<33.5%) of plasma cells. The presence or absence of immature plasma cells has no significant impact on the survival of MM patients.
Humans
;
Multiple Myeloma/pathology*
;
Prognosis
;
Plasma Cells/cytology*
;
Retrospective Studies
;
Male
;
Female
;
Middle Aged
;
Aged
;
Bone Marrow
10.Clinical Characteristics and Prognosis of 7 Patients with T-Cell Large Granular Lymphocytic Leukemia.
Yong-Qian ZHANG ; Yuan-Yuan ZHANG ; Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Qiao-Lin CHEN ; Qi-Ke ZHANG ; Ji-Sheng ZHAO
Journal of Experimental Hematology 2025;33(3):706-710
OBJECTIVE:
To analyze the clinical characteristics and prognosis of patients with T-cell large granular lymphocytic leukemia (T-LGLL).
METHODS:
The clinical data of 7 patients with T-LGLL in Gansu Provincial Hospital from March 2016 to June 2023 were analyzed retrospectively.
RESULTS:
Among the 7 patients, 5 were male and 2 were female, with a median age of 51(28-83) years old. At the onset of illness, 6 cases showed symptoms of fatigue and anemia, 4 cases had enlarged lymph nodes, and 5 cases had splenomegaly. Examination showed that 4 cases were antinuclear antibody(ANA) positive, 5 cases were anemia. The median hemoglobin (Hb) level was 83(61-151) g/L, the median white blood cell count (WBC) was 5.6(2.0-8.7)×109 /L, and the median percentage of lymphocytes in peripheral blood was 66.2(13.9-89.1)%. There were 3 cases with extremely active bone marrow hyperplasia, 2 cases with active hyperplasia, and 2 cases with decreased hyperplasia. There were 5 cases with mild myelofibrosis (MF-1), and 1 case with moderate myelofibrosis (MF-2). The median percentage of T cells was 64.3 (31.5-80.6)%. 5 cases showed the classic immunophenotype (CD3 + CD4- CD8 +), 6 cases were CD57 +, 3 cases were TCRα/β +, and 3 cases were TCRγ/δ +. TCRG rearrangement was detected in 5 cases.The median follow-up time was 55(4-87) months, one patient died of heart disease, and the other 6 patients are surviving.
CONCLUSION
The incidence of T-LGLL is low. The initial symptoms of T-LGLL include anemia, fatigue, lymph node enlargement, splenomegaly, and higher percentage of lymphocytes in peripheral blood, the percentage of abnormal T cells in bone marrow was significantly increased. Analysis of flow cytometric immunophenotyping, TCR gene rearrangement, and hot spot genes such as STAT3 and STAT5b, can improve the diagnostic accuracy.
Humans
;
Leukemia, Large Granular Lymphocytic/diagnosis*
;
Male
;
Middle Aged
;
Female
;
Aged
;
Prognosis
;
Adult
;
Aged, 80 and over
;
Retrospective Studies

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