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.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, with few effective treatments currently available. The multifactorial nature of AD, shaped by genetic, environmental, and biological factors, complicates both research and clinical management. Recent advances in artificial intelligence (AI) and multi-omics technologies provide new opportunities to elucidate the molecular mechanisms of AD and identify early biomarkers for diagnosis and prognosis. AI-driven approaches such as machine learning, deep learning, and network-based models have enabled the integration of large-scale genomic, transcriptomic, proteomic, metabolomic, and microbiomic datasets. These efforts have facilitated the discovery of novel molecular signatures and therapeutic targets. Methods including deep belief networks and joint deep semi-non-negative matrix factorization have contributed to improvements in disease classification and patient stratification. However, ongoing challenges remain. These include data heterogeneity, limited interpretability of complex models, a lack of large and diverse datasets, and insufficient clinical validation. The absence of standardized multi-omics data processing methods further restricts progress. This review systematically summarizes recent advances in AI-driven multi-omics research in AD, highlighting achievements in early diagnosis and biomarker discovery while discussing limitations and future directions needed to advance these approaches toward clinical application.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in Fusobacterium nucleatum (Fn), which binds Fn-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed that in both the Fn type strain and a clinical tumor isolate, deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition. Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Furthermore, AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA. By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs (sRNAs), our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
Fusobacterium nucleatum/growth & development* ; RNA-Binding Proteins/genetics* ; Bacterial Proteins/genetics* ; RNA, Bacterial/metabolism* ; Humans ; RNA, Transfer/metabolism*

OBJECTIVE To investigate the use of common disposable and reusable supplies for prevention and con-trol of infections in Shanghai.METHODS A survey was conducted for the use and reuse of disposable high-value consumables,disposable bronchoscopes and environmental cleaning and disinfection tools in Shanghai by using structured questionnaire.RESULTS Totally 81 medical institutions were involved in the survey,44(54.32％)of which were tertiary hospitals,and the median number of beds was 500.The orthopedic implants(70.37％),ul-trasound knife(69.14％)and endoscopic puncture instrument(66.67％)were the high-value consumables rank-ing the top 3 utilization rates.There was reuse of 18 types of high-value consumables in total among the 12 medi-cal institutions.The major causes of reuse of high-value consumables included fee less tan cost of consumables(58.33％)or being unable to included in charge items(33.33％).27.78％of the recycle high-value consumables were not treated with a dedicated disinfection and sterilization system and procedures for the disposable high-value consumables,and 33.33％did not have the report systems for related adverse reactions.49.09％of the medi-cal institutions reported to use the disposable bronchoscopes,4 of which reused them.The majority of the medi-cal institutions could carry out centralized cleaning and disinfection for the recycled floor cloths(60.81％)and cloth towels(56.76％),and 32.43％of the medical institutions reused the cloth towels by manual cleaning.The utilization rate of antiseptic wipes was 75.41％in adult intensive care unit,62.50％in neonatal intensive care unit.CONCLUSION The study reveals that there are some problems in the use of disposal and reusable supplies for prevention and control of infections,which may provide baseline data for management of the related supplies and the surveillance of disinfection of the recycled supplies so as to enhance the quality of management of hospital-asso-ciated infections.

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: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.

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.