Introduction: Chronic tophaceous gout is a rare cause of parathyroid hormone (PTH)-independent hypercalcemia. This is due to increased 1-alpha hydroxylase activity within granulomatous inflammation surrounding gouty tophi, resulting in excess calcitriol production. In advanced disease, immobilization from pain and joint deformity may further exacerbate hypercalcemia due to immobilizationrelated bone resorption, leading to clinically significant symptoms and complications. Case: A 59-year-old male with chronic tophaceous gout complicated with CKD and nephrocalcinosis was referred for inpatient evaluation of hypercalcemia. He had an episode of acute pancreatitis attributed to hypercalcemia 1 month prior. Serum calcium levels have risen progressively over the preceding year, from 2.48 mmol/L (reference 2.0–2.65) to 3.17 mmol/L. His gout was poorly controlled with uric acid levels ranging 641–709 umol/L, with extensive tophi over the upper and lower limbs and gluteal regions. He had been maintained on low-dose allopurinol 150 mg/day for 2 years. Functionally, he was largely bedbound and wheelchair-dependent. On admission, corrected calcium was 3.48 mmol/L with suppressed intact parathyroid hormone (<0.6 pmol/L) consistent with PTH-independent hypercalcemia. Malignancy and myeloma workup, including tumor markers, was unremarkable. Serum phosphate (0.9 mmol/L) and alkaline phosphatase (152 IU/L) were normal. Hypercalcemia persisted despite intravenous hydration and calcitonin. Low-dose prednisolone was then initiated, followed by pamidronate, resulting in normalization of corrected calcium to 2.17 mmol/L. He remained normocalcemic while on tapering prednisolone for a month. However, calcium rebounded months after cessation. Gradual escalation of allopurinol to 900 mg/day improves uric acid levels to 389–429 umol/L with better functional status (standing unsupported briefly and mobilizing with assistance). However, calcium remains moderately elevated 2.65–2.85 mmol/L. Conclusion This case highlights severe tophaceous gout as a rare but significant cause of PTH-independent hypercalcemia, in which glucocorticoids can be effective in treating refractory hypercalcemia. It also underscores the importance of addressing the underlying disease through optimization of urate-lowering therapy and functional rehabilitation.

Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

Objective To investigate the predictive value of four thrombotic markers[thrombin-antithrombin complex(TAT),tissue-type plasminogen activator-plasminogen activator inhibitor-1 complex(t-PAIC),plasmin-α2-plasmin inhibitor complex(PIC)and thrombomodulin(TM)]for short-term prognosis of patients with acute leukemia complicated by disseminated intravascular coagu-lation(DIC).Methods A prospective cohort study was conducted.Fifty-two patients with acute leukemia complicated by DIC were selected as study group,and 50 patients with simple acute leuke-mia were selected as control group.The general data and levels of the four thrombotic markers(PIC,TAT,TM,t-PAIC)were compared between the two groups.The Kaplan-Meier(KM)survival curve was plotted to analyze the 28-day prognosis of the patients in the study group.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of the four thrombotic markers for poor short-term prognosis in patients with acute leukemia complicated by DIC.Results The plas-ma levels of TAT,PIC,t-PAIC and TM in the study group were higher than those in the control group,and the differences were statistically significant(P＜0.05).Among the patients in the study group,there were 17 deaths(poor prognosis)and 35 survival cases(good prognosis)at 28 days.The plas-ma levels of TAT,PIC,t-PAIC and TM in patients with poor prognosis were higher than those in pa-tients with good prognosis at admission,and the differences were statistically significant(P＜0.05).The ROC curve showed that the area under the curve(AUC)for TAT,PIC,t-PAIC,and TM in predicting poor short-term prognosis in patients with acute leukemia complicated by DIC alone were 0.775,0.769,0.767,and 0.770,respectively.The AUC for the combined prediction of the four thrombotic markers was 0.939,which was higher than that for each individual marker(Z=1.986,2.014,2.026,2.003;P=0.021,0.010,0.008,0.014).Conclusion The four thrombotic markers(TAT,PIC,t-PAIC,TM)have a high predictive value for the short-term prog-nosis of patients with acute leukemia complicated by DIC.Combined detection can provide a refer-ence basis for clinical prognosis prediction in these patients.

Objective A cross-sectional survey on the postoperative home care status and barriers was conducted among elderly patients with osteoporotic fractures nationwide,in order to provide a basis for promoting the improvement of standardized home care for elderly patients with osteoporotic fractures.Methods From October to November 2023,a survey on the current situation and barriers of home environment protection was conducted among elderly patients with osteoporotic fractures in the orthopedic wards of 594 hospitals across 31 provinces(autonomous regions/municipalities directly under the central government)using a convenience sampling method.Results A total of 14,349 questionnaires were distributed,and 12,496 valid questionnaires were collected,resulting in an effective response rate of 87.09％.Among the patients,5,502 cases(44.03％)had implemented home-based prevention and treatment of osteoporosis before the fracture.2 095(16.77％)of the patients experienced a subsequent fracture,of which 65.11％of the patients who experienced a subsequent fracture received medication intervention after the initial fracture,while 19.86％of the patients who experienced a subsequent fracture did not comply with the treatment for osteoporosis after the initial fracture.Additionally,77.66％(n=1 627/2 095)of the patients received community medical services after the initial fracture.Barriers to care factors in the home environment after fracture from the patient's perspective presented the complexity of the social-ecological system model in 6 dimensions at 2 levels:micro(basic personal situation,physiological factors,psychological factors,and behavioural factors),and meso(social support factors,and healthcare worker factors).Conclusion In the vast majority of elderly patients in China,before osteoporotic fracture,home-based measures to prevent osteoporosis have not been adequately implemented;after the initial osteoporotic fracture,the pathway of re-fracture prevention and management in the patient's home environment is not yet complete and its popularity needs to be improved;the barriers to home care faced by elderly patients with osteoporotic fracture are complex.It is recommended to promote effective linkages among hospitals,community health centres and families to strengthen the closed-loop management of re-fracture prevention and management.

Objective:To explore the influence of non-motor symptoms on the change trajectory of early activities of daily living in patients with Parkinson disease, and to provide a reference for medical staff to implement intervention measures for people with low levels of activities of daily living in the preclinical stage.Methods:The longitudinal follow-up data of 431 patients with Parkinson disease in the Parkinson's progression Markers Initiative from baseline to five consecutive years after enrollment were selected by convenience sampling method in July 2024, including the scores of aceivities of daily living, the Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire, etc. A latent class growth model classified change trajectory of activities of daily living, and the influencing factors were analyzed by univariate and binary Logistic regression.Results:Among the 431 patients, 260 were male and 171 were female, with an average age of (61.30 ± 9.60) years. The scores of activities of daily living of the patients at baseline, 12 months after enrollment, 36 months after enrollment, and 60 months after enrollment were (5.97 ± 4.30), (7.20 ± 4.61), (8.90 ± 5.60), and (10.57 ± 6.93) points, respectively. The model identified two types of trajectories: rapid decline in low activities of daily living group (25.3%, 109/431) and slow decline in lower activities of daily living group (74.7%, 322/431). The binary Logistic regression results showed that apathy ( OR=0.374, 95% CI 0.189-0.739), fatigue ( OR=0.261, 95% CI 0.138-0.495), University of Pennsylvania Smell Identification Test ( OR=1.039, 95% CI 1.005-1.074), the Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire ( OR=0.880, 95% CI 0.795-0.973), and the gastrointestinal score of the Scales for Outcomes in PD-Autonomic ( OR=0.724, 95% CI 0.630-0.832) were independent influencing factors for the classification of the change trajectory of activities of daily living in patients with Parkinson disease (all P<0.05). Conclusions:Patients with Parkinson disease exhibit a decreasing trend in early activities of daily living, emphasizing the need for targeted interventions in those with fatigue, apathy, and high Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire and Scales for Outcomes in Parkinson disease-Autonomic gastrointestinal scores to possibly decelerate disease advancement.

Objective:This study analyzed the clinical characteristics and early mortality risk factors in patients with hyperleukocytic acute leukemia (HAL) to provide a basis for predicting early prognosis.Methods:Data were retrospectively collected from 211 patients with primary HAL who visited the Emergency Center of the Hematology Hospital, Chinese Academy of Medical Sciences, between July 1, 2019 and November 30, 2021. The value of each indicator in early risk stratification and prognosis was analyzed.Results:The early-death group exhibited higher WBC, peripheral blood immature cell proportions, prothrombin times (PT), fibrinogen degradation products (FDP), and D-dimer levels than the non-early death group ( P<0.05). Mortality in hyperleukocytic AML (20.5% ) was significantly higher than that in hyperleukocytic ALL (9.3% ) ( P<0.05). There were significant differences in age, creatinine, PT, fibrinogen (FIB) levels, WBC, lactic dehydrogenase (LDH), uric acid, blood potassium, blood calcium, and blood phosphorus levels between the two groups of patients ( P<0.05). A WBC threshold of 255.96×10?/L predicted early mortality with 65.6% sensitivity and 69.0% specificity, with higher WBC levels associated with a 5.164-fold increased mortality risk ( P<0.05). The age, WBC, LDH, urea, PT, FDP and D-dimer of patients at the time of consultation are risk factors affecting the survival of HAL ( P<0.05) . Conclusion:HAL is a life-threatening condition with a high early mortality. Age, WBC, LDH, urea, PT, FDP and D-dimer are risk factors for early death in HAL.

Toll-like receptor 5(TLR5)is a pattern recognition receptor,the main extracellular receptor for recognizing flagel-lin,and a bridge between innate and adaptive immunity.It can activate innate immunity and induce the release of a series of down-stream cytokines,as well as play an important role in protecting the host from flagellated pathogens and establishing immune tolerance.These functions are related to the pathogenesis of obesity hypertension in various aspects.This article aims to review the relationship between TLR5 and obese hypertension,as well as the new progress on the interaction between TLR5 and flagellin structure and func-tion,and discuss the future research directions and challenges.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To compare the efficacy of biplanar fixation combined with bone grafting and proximal femoral nail anti-rotation (PFNA) in the treatment of critically complicated osteoporotic intertrochanteric femoral fracture .Methods:A retrospective cohort study was conducted to analyze the clinical data of 28 patients with critically complicated osteoporotic intertrochanteric femoral fracture, admitted to Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 2020 and December 2022, including 3 males and 25 females, aged 70-91 years [(79.4±6.3)years]. T score for bone mineral density was -2.5~-4.1 SD［（-3.3±0.6）SD］. All the patients were found with type A2.2-A3.3 fracture based on AO classification, and were complicated with trochanteric lateral wall fracture. Among them, 16 patients underwent biplanar fixation combined with bone grafting (biplanar fixation group), while 12 underwent PFNA internal fixation (PFNA group). All the patients received anti-osteoporosis therapy after surgery. The two groups were compared in terms of the operative time, intraoperative blood loss, hemoglobin levels at 3 days postoperatively, and time to weight-bearing. The visual analogue scale (VAS) scores and Harris hip scores at 1, 3, 6 months postoperatively, and at the last follow-up and the incidence of complications were also detected in the two groups.Results:All the patients were followed up for 12-16 months [(14.1±1.4)months]. In the biplanar fixation group, the operative time was (75.1±15.3)minutes, significantly longer than (45.6±14.2)minutes in the PFNA group ( P<0.01); the intraoperative blood loss was (234.1±11.8)ml, significantly more than (170.0±13.4)ml in the PFNA group ( P<0.01); the hemoglobin level at 3 days postoperatively was (82.6±9.3)g/L in the biplanar fixation group, higher than (64.8±6.8)g/L in the PFNA group ( P<0.01). The time to weight-bearing was (1.1±0.7)weeks in the biplanar fixation group, significantly shorter than (3.2±1.2)weeks in the PFNA group ( P<0.01). There were no statistically significant differences between the two groups in VAS scores and Harris hip scores at 1, 3, 6 months postoperatively, and at the last follow-up ( P>0.05). The VAS scores and Harris hip scores in the two groups were gradually improved with the prolongation of postoperative time ( P<0.05 or 0.01). No complications such as neurovascular injuries were observed in either group. One patient in the biplanar fixation group developed lower extremity deep vein thrombosis (DVT), with a complication rate of 6.3%, while 2 patients in the PFNA group developed lower extremity DVT and 4 hypostatic pneumonia, with a complication rate of 50.0% ( P<0.05). Conclusion:Compared with PFNA internal fixation, biplanar fixation with bone grafting has the advantages of less postoperative blood loss, earlier weight-bearing exercises and lower incidence of complications in the treatment of critically complicated osteoporotic intertrochanteric femoral fracture, despite longer operative time and more intraoperative blood loss.