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 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 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: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.

An 8-year-old male child with acute lymphoblastic leukemia(ALL)developed signs of methotrexate(MTX)toxicity—such as vomiting,chest tightness,and rapidly elevated serum creatinine and uric acid levels—on the second day after his first high-dose methotrexate(HD-MTX)treatment.The toxicity is considered due to delayed excretion of methotrexate.The clinical pharmacist assisted the medical team in formulating a treatment plan that included adequate hydration and alkalinization,leucovorin rescue,and subsequent dose adjustment of MTX,based on therapeutic drug monitoring and pharmacogenetic testing results.By day 11,the patient's MTX plasma concentration,serum creatinine,and uric acid levels had returned to safe ranges.In this case,the clinical pharmacists used pharmaceutical knowledge to analyze potential factors contributing to delayed MTX elimination,and assisted the treatment team to improve the safety and efficacy of drug therapy.This case provides valuable experience for the standardized management of similar pediatric patients.

An 8-year-old male child with acute lymphoblastic leukemia(ALL)developed signs of methotrexate(MTX)toxicity—such as vomiting,chest tightness,and rapidly elevated serum creatinine and uric acid levels—on the second day after his first high-dose methotrexate(HD-MTX)treatment.The toxicity is considered due to delayed excretion of methotrexate.The clinical pharmacist assisted the medical team in formulating a treatment plan that included adequate hydration and alkalinization,leucovorin rescue,and subsequent dose adjustment of MTX,based on therapeutic drug monitoring and pharmacogenetic testing results.By day 11,the patient's MTX plasma concentration,serum creatinine,and uric acid levels had returned to safe ranges.In this case,the clinical pharmacists used pharmaceutical knowledge to analyze potential factors contributing to delayed MTX elimination,and assisted the treatment team to improve the safety and efficacy of drug therapy.This case provides valuable experience for the standardized management of similar pediatric patients.

Objective To explore the influence of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with brain-computer interface rehabilitation robot in patients with upper limb motor dysfunction after stroke.Methods A total of 126 patients with upper limb motor dysfunction after stroke were divided into the combined group(61 cases,low-frequency rTMS combined with brain-computer interface rehabilitation robot on the basis of routine rehabilitation treatment)and the magnetic stimulation group(65 cases,low-frequency rTMS on the basis of routine rehabilitation treatment)according to different treatment methods,and both groups were continuously treated for 3 weeks.The upper limb motor function[upper-extremity Fugl-Meyer scale(UFMA),action research arm test(ARAT)],hand Brunnstrom staging,upper limb surface electromyography indicators[root mean square(RMS)and integrated electromyography(iEMG)of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle],cerebral artery hemodynamics[systolic blood flow velocity(Vs),resistance index(RI),mean blood flow velocity(Vm)]and ratio of fractional anisotropy(FA)of central region of brain lesion and FA of mirror-image region of healthy cerebral hemisphere(rFA)were observed before and after treatment in the two groups.Results Compared with the magnetic stimulation group,the UFMA score,ARAT score,hand Brunnstrom staging,Vs,Vm and rFA were higher after treatment in the combined group(P＜0.05).The RMS and iEMG of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle were higher in the combined group compared with those of the magnetic stimulation group(P＜0.05),while the RI was lower(P＜0.05).Conclusion Combined treatment can more effectively improve the upper limb motor function of patients,enhance hand activity ability,promote the recovery of upper limb muscle and nerve function,and regulate the hemodynamics of cerebral arteries.

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 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.