OBJECTIVE To conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

OBJECTIVE To evaluate the safety of fondaparinux in pregnancy and provide reference for its rational clinical application. METHODS A search was conducted in databases including CNKI， Wanfang， PubMed， Embase， and Elsevier （the search time was from the construction of the database to December 17， 2024） to collect case report literature on fondaparinux use during pregnancy. Patient demographic information， fondaparinux use during pregnancy， concomitant medications， clinical manifestations， and treatment details were extracted for descriptive statistical analysis. RESULTS A total of 17 case reports regarding the use of fondaparinux during pregnancy were collected， involving 42 patients from 11 countries and 47 pregnancy records. Among these， 20 cases involved the use of fondaparinux for the prevention of pregnancy-related venous thromboembolism （VTE）， while 27 cases were fondaparinux treatment due to related conditions. A total of 29 occurrences of the patients were treated with fondaparinux due to a （family） history of VTE. Nine occurrences of complicated pregnancies were reported， and 35 patients had records of comorbidities or relevant medical histories. The adverse events that occurred during pregnancy with the use of fondaparinux include postpartum hemorrhage （7 cases） and excessive anticoagulation caused by inappropriate dosage （1 case）. Among the 7 cases of postpartum hemorrhage， 3 cases had a blood loss of no less than 1 000 mL （including 2 cases with uterine atony）， 3 cases had a drug discontinuation time of ≤12 h. CONCLUSIONS Based on the existing literature， the safety of fondaparinux during pregnancy is generally manageable， with the main adverse event being postpartum hemorrhage. The dosage， interval between discontinuation，comorbidities/medical history， and concomitant medications of fondaparinux may be the main causes of its adverse events.

This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

Objective: To investigate the Alzheimer's disease (AD) influencing factors among the elderly, so as to provide a basis for early prevention and intervention. Methods: From March to June 2024, participants aged 60 years and above from a sub-district in Haishu District, Ningbo City, Zhejiang Province were selected using a convenience sampling method. Data on demographics, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were evaluated using the short-form Geriatric Depression Scale. The Chinese Mini-Mental State Examination (MMSE) was used for the initial screening of AD, and individuals who screened positive were further diagnosed by psychiatrists. Factors affecting AD among the elderly were analyzed using a multivariable logistic regression model. Results: A total of 3 644 individuals were surveyed, comprising 1 526 males (41.88%) and 2 118 females (58.12%). The mean age was (71.85±7.44) years. AD was detected in 200 cases, with a detection rate of 5.49%. Multivariable logistic regression analysis showed that individuals aged ≥65 years (65-<70 years, OR=3.012, 95%CI: 1.007-9.012; 70-<75 years, OR=3.131, 95%CI: 1.059-9.260; 75-<80 years, OR=5.779, 95%CI: 1.989-16.784; ≥80 years, OR=16.810, 95%CI: 5.926-47.685), those who were unmarried, divorced, or widowed (OR=1.973, 95%CI: 1.383-2.815), those with hearing loss (OR=1.573, 95%CI: 1.128-2.193), those with diabetes mellitus (OR=1.958, 95%CI: 1.362-2.814), and those with depressive symptoms (OR=4.143, 95%CI: 2.997-5.728) had a higher risk of AD. Conversely, individuals with an educational level of primary school or above (primary school, OR=0.579, 95%CI: 0.401-0.835; junior high school or above, OR=0.438, 95%CI: 0.259-0.741), and those who engaged in regular physical exercise (OR=0.414, 95%CI: 0.264-0.649) had a lower risk of AD. Conclusions The detection rate of AD was relatively high among the elderly in Haishu District. AD among the elderly was related to age, educational level, marital status, physical exercise, hearing loss, diabetes mellitus, and depressive symptoms.

OBJECTIVE: To investigate the clinical characteristics, curative effect and prognostic factors of patients with multiple myeloma (MM) complicated with light chain myocardial amyloidosis (AL-CA). METHODS: The data of 38 patients diagnosed with MM complicated with AL-CA in our hospital from January 2018 to December 2023 were retrospectively analyzed, and the data were comprehensively screened by multiple methods such as positive two-dimensional spot tracking echocardiography (2D-STE). Survival analysis was performed using the Kaplan-Meier method. Cox regression models were used to screen for independent prognostic factors. RESULTS: Among the 38 MM patients with AL-CA, 23 were male and 15 were female, with a median age of 60(50,75) years. The 1-year survival rate was 71.05%. Patients who underwent transplantation had significantly better survival outcomes than those who did not (P < 0.01). Additionally, the median survival time of patients with all-negative FISH results at the first visit was statistically different compared to patients with other mutations (P < 0.05). Multivariate Cox regression analysis showed that all negative FISH results at the first visit and the absence of autologous hematopoietic stem cell transplantation (ASCT) were not independent risk factor for the prognosis of patients with MM and AL-CA (P >0.05). CONCLUSION ASCT may improve the prognosis of MM patients with AL-CA, and negative FISH results may indicate poor prognosis, but the results still need to be verified by larger samples.
Humans ; Multiple Myeloma/complications* ; Retrospective Studies ; Aged ; Female ; Male ; Middle Aged ; Prognosis ; Hematopoietic Stem Cell Transplantation ; Amyloidosis/complications* ; Survival Rate ; Proportional Hazards Models

Objective： To analyze the symptoms, diagnosis and treatment of upper urinary tract calculi patients combined with mild and moderate benign prostatic hyperplasia (BPH) after ureteral stent implantation. Methods： One hundred and six BPH patients who were hospitalized for upper urinary tract calculi and had ureteral stents retained from January 2019 to December 2022 were selected and divided into 2 weeks group and 4 weeks group according to the time of removal of ureteral stents after surgery. Their general clinical data were analyzed and compared. International Prostatic Symptom Scale (IPSS), postoperative ureteral Stent Symptom Questionnaire (USSQ), and incidence of adverse events after ureteral stent removal were recorded before and after removal. Results： The scores of IPSS were significantly increased in all patients, and symptoms in urinary tract had improved significantly after discharge (P<0.05). Compared with the 2 weeks group, the USSQ score of the 4 weeks group was significantly increased (P<0.05). And no significant adverse event was observed in the 2 weeks group after the removal of ureteral sten. Conclusion： IPSS score and USSQ score increased significantly during stent implantation in BPH patients with lithiasis. And complications increased significantly over time. Following thorough clinical assessment, early ureteral stent removal demonstrates both safety and efficacy, representing an optimal therapeutic approach in selected cases.
Humans ; Male ; Prostatic Hyperplasia/surgery* ; Stents ; Ureter/surgery* ; Aged ; Middle Aged ; Urinary Calculi/surgery* ; Ureteral Calculi/surgery*

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Objective To prepare polymersomes (PSs) by block copolymers，evaluate their membrane structural stability，investigate the H⁺ transmembrane permeability of PSs and the impact of 1,4-dioxane and establish a foundation for drug encapsulation within polymersomes. Methods PSs were self-assembled by a block copolymer, PEG-PLGA, in a solvent solution. The pH-sensitive fluorescence probe HPTS was employed to examine the H⁺ transmembrane properties of PSs and compare them with PSs prepared using PBD-b-PEO, PS-b-PEO, and liposomes. The effect of varying concentrations of 1,4-dioxane on PSs’ membrane permeability properties was also investigated. Results The fluorescence excitation spectra of HPTS exhibited pH dependency, which showed a linear correlation between extravesicular H⁺ concentration and t^1/2. Significant differences were observed in the membrane permeability capabilities of PSs with different membrane wall thicknesses. Compared to liposomes, the H⁺ transmembrane coefficients for the three types of PSs were reduced by 2.39×10⁴, 3.38×10⁴, and 5.48×10⁸ times, respectively. 1,4-dioxane was found to modulate the permeability of PSs’ membranes, which displayed a concentration-dependent relationship. Conclusion PSs exhibited significantly lower membrane permeability compared to liposomes, indicating superior stability. 1,4-dioxane was identified as a modulator of PSs’ permeability, which offered potential for drug loading and release within PSs.

Objective:To analyze and explore the effect of dapagliflozin on cardiac function,mitogen activated protein ki-nase(MAPK),inducible nitric oxide synthase(iNOS)and extracellular regulated protein kinase 1/2(ERK1/2)in patients with severe heart failure(SHF).Methods:A total of 122 SHF patients treated in our hospital were selected,randomly and equally divided into routine treatment group(received diuretic vasodilation-dominant basic therapy)and dapagliflozin group(received dapagliflozin based on routine treatment group).After three-month treatment,therapeutic effect,cardi-ac function,coronary hemodynamic indexes and therapeutic safety were compared between two groups.Results:The total effective rate of dapagliflozin group was significantly higher than that of routine treatment group(91.80％vs.77.05％,P=0.025).Compared with routine treatment group after treatment,there were significant rise in left ventricular ejection fraction(LVEF),stroke volume(SV),diastolic peak velocity(DPV),systolic peak velocity(SPV)and coronary blood flow(CBF),and significant reductions in QT interval dispersion(QTd),left ventricular end-diastolic diameter(LVEDd),coronary resistance(CR)and levels of MAPK[(46.79±7.02)ng/L vs.(39.38±5.82)ng/L],iNOS[(88.93±10.02)μmol/L vs.(79.61±9.04)μmol/L]and ERK1/2[(27.03±5.83)ng/L vs.(21.62±4.18)ng/L]in dapagliflozin group,P=0.001 all.There was no significant difference in incidence rate of adverse reactions between two groups,P=0.408.Conclusion:Dapagliflozin combined with diuretic and vasodilator therapy has a significant therapeutic effect on patients with severe heart failure,which can improve cardiac function and coronary hemodynamics,reduce the levels of MAPK,iNOS,and ERK1/2 with good safety.

Objective To formulate a pharmaceutical service pathway to standardize the pharmacists'whole process of pharmaceutical services for breast cancer patients in medical institutions,promote the standardization of pharmacists'work and improve the rationality of drug use for breast cancer patients in medical institutions.Methods The editorial committee aimed at several challenging problems in the whole process of pharmaceutical services for breast cancer patients in medical institutions through systematic search,referring to the latest domestic and international guidelines and expert consensus of breast cancer and under the relevant drug administration regulations in China,collected and sorted out the professional opinions of doctors,pharmacists,and methodological experts,developed questionnaires and held two rounds of expert argumentation meetings,and finally screened out the most valuable results.The whole process management pathway of pharmaceutical care for breast cancer patients was formulated,and the referral principles of hospitals at different levels and the contents of pharmacist training and assessment were clarified.Results The whole process management pathway of pharmaceutical services for breast cancer patients was developed,including information collection,analysis,evaluation,development implementation of intervention plans,and follow-up.Conclusion This pharmaceutical service pathway can standardize and guide pharmacists in hospitals at different levels to carry out pharmaceutical services for breast cancer patients,achieve the whole process of monitoring drug use,and ensure rational drug use and treatment effectiveness for patients.