Autoimmune diseases （AIDs） are chronic inflammatory disorders in which the immune system mistakenly attacks self-tissues. Conventional treatments rely on non-specific immunosuppression or targeted anti-inflammatory agents to control symptoms but do not offer a cure. The 2025 Nobel Prize， awarded for discoveries on regulatory T cells （Tregs） and peripheral immune tolerance， has revealed that AIDs pathogenesis involves not only excessive effector cell activation but also defective Treg-mediated regulation. Consequently， the therapeutic goal is evolving from long-term inflammation suppression to active re-establishment of immune tolerance. This review elaborates current strategies toward this goal， including Treg-targeted therapies， antigen-specific immune tolerance induction， and deep immune-reset approaches such as chimeric antigen receptor T cell （CAR-T） therapy. It also introduces the "sequential immunotherapy" framework，which integrates the strategies through three-stage process of rapid inflammation control， deep immune reset， and active tolerance induction to restore immune homeostasis. Although challenges remain in safety， patient heterogeneity， and accessibility， advances in precision medicine and cell engineering hold promise for shifting AIDs treatment toward immune tolerance restoration and durable drug-free remission.

Critically ill patients often experience hemodynamic instability， hypoalbuminemia， and altered renal function， which significantly alter the distribution and clearance of carbapenem antibiotics. Conventional dosing regimens are therefore prone to result in either subtherapeutic exposure or overdosing. Therapeutic drug monitoring （TDM）， by measuring plasma drug concentrations and integrating the minimum inhibitory concentration （MIC） to establish pharmacokinetic/pharmacodynamic （PK/PD） targets， provides a basis for individualized dosing. The optimal PK/PD index for carbapenems is the percentage of time that free drug concentration exceeds MIC（%fT >MIC）， with a recommended target of 100% fT ≥MIC， and 100% fT ≥4×MIC may also be considered. With intermittent or extended intravenous infusion regimens， these target values may approximately correspond to steady-state trough concentrations ≥MIC or 4×MIC. For continuous infusion， steady-state free concentrations can be used instead of trough concentrations.In addition， factors such as protein binding rate， timing of blood sampling， and changes in renal function should be taken into account， forming a complete cycle of "target setting—TDM monitoring—result interpretation—dose adjustment — reassessment". This review focuses on PK/PD targets， the conversion from target values to plasma concentrations， and dose adjustment strategies of carbapenem antibiotics in critically ill patients， aiming to provide a reference for clinical individualized dosing.

CD388 is a first-in-class long-acting anti-influenza virus drug developed by Cidara Therapeutics. It is composed of linking a derivative of zanamivir with the Fc fragment of human IgG1 antibody through a linker. It utilizes the intracellular recycling mechanism mediated by the neonatal Fc receptor to extend the in vivo half-life to several weeks. A single subcutaneous injection can cover the entire influenza epidemic season. Current clinical evidence indicates that CD388 has good effectiveness， safety and tolerability in influenza prevention， and presents ideal pharmacokinetic characteristics. In October 2025， based on the positive results of the published Phase IIb NAVIGATE clinical study， FDA granted it Breakthrough Therapy Designation for the prevention of seasonal influenza. Currently， the key Phase Ⅲ ANCHOR study of CD388 is underway. This article provides an overview of the basic information， mechanism of action， preclinical research， and clinical research of CD388.

Insomnia is the most common sleep disorder， characterized by difficulty in falling asleep，difficulty in maintaining sleep， or early morning awakening. Long-term use of traditional benzodiazepine and non-benzodiazepine sedative-hypnotics has limitations including dependence， drug tolerance， and withdrawal rebound. The orexin system serves as the core pathway regulating wakefulness， and blocking excessive arousal signals to restore sleep has emerged as a new direction for insomnia treatment. Fazamorexant is a domestically developed dual orexin receptor antagonist indicated for adult insomnia with difficulty in sleep onset and/or sleep maintenance.This article summarizes the pharmacological mechanism， pharmacokinetic profile， clinical efficacy， and safety data of fazamorexant， and reviews the considerations for use in special populations as well as the limitations of current evidence.

Objective To investigate the effect of tranexamic acid on the incidence of postoperative delirium （POD） in elderly patients undergoing hip or knee arthroplasty. Methods A total of elderly patients undergoing elective hip or knee arthroplasty from January to August 2025 were enrolled and randomly divided into the tranexamic acid group （observation group） and the normal saline control group （control group）. The observation group received an intravenous infusion of tranexamic acid 1 g 15 minutes before skin incision， while the control group received an equal volume of normal saline at the same time point， with both groups completing the infusion before incision. The 3-Minute Diagnostic Interview for Confusion Assessment Method was used to assess the incidence of POD within 3 days postoperatively and other related indicators. Results A total of 198 patients were included，with 100 in the observation group and 98 in the control group.The incidence of POD was 9.00% in the observation group and 21.43% in the control group C， with a significant between-group difference （P<0.05）. Compared with the control group， the observation group had a lower incidence of cognitive impairment within 3 days postoperatively （P<0.05）， lower serum IL-6 levels at 24 h postoperatively （P<0.001）， and reduced intraoperative blood loss （P<0.05）. No significant between-group differences were observed in pain scores， 15-item quality of recovery scores， intraoperative fluid intake and output， vasoactive drug use， MAP and HR at each time point， and the incidence of perioperative adverse events （P > 0.05）. Conclusion In elderly patients， preoperative intravenous tranexamic acid is associated with a lower incidence of POD and postoperative cognitive impairment within 3 days postoperatively. These effects may be related to reduced intraoperative blood loss and lower postoperative serum IL-6 levels.

Objective To investigate the association of tirofiban sequential dual antiplatelet therapy with neurological outcomes in patients with acute anterior circulation small artery occlusion ischemic stroke. Methods Patients with acute anterior-circulation small-artery occlusion ischemic stroke admitted to the Fifth Affiliated Hospital of Anhui Medical University from September 2020 to February 2026 were retrospectively enrolled and divided according to the antiplatelet regimen actually received during hospitalization into the tirofiban sequential dual antiplatelet group and the conventional dual antiplatelet control group. One-to-one propensity score matching （PSM） was used to balance baseline characteristics. Neurological improvement at 72 h， early neurological deterioration （END）， 90-day functional outcome， recurrent ischemic stroke， and bleeding events were compared， and factors associated with favorable 90-day functional outcome were analyzed in the samples after PSM. Results A total of 101 patients were included （60 in the tirofiban group and 41 in the control group）， and 39 matched pairs were obtained. At 72 h， the tirofiban group had a lower NIHSS score （2.74±1.83 vs. 3.66±2.13）， a greater NIHSS reduction （2.36±1.64 vs. 1.36±1.48）， and a higher neurological improvement rate （74.36% vs. 48.72%； all P<0.05）. END occurred in 7.69% versus 25.64% of patients （two-sided Fisher exact P=0.065）. Favorable 90-day outcome occurred in 84.62% versus 64.10% （P=0.038）. Multivariable logistic regression showed that tirofiban followed by dual antiplatelet therapy was associated with a higher likelihood of favorable 90-day outcome （OR=4.788， 95%CI：1.251-18.331，P=0.022）， whereas older age and a higher admission NIHSS score were associated with a lower likelihood of favorable outcome （both P<0.05）. No symptomatic intracranial hemorrhage occurred， and recurrent stroke or bleeding events did not differ significantly between groups. Conclusion Tirofiban followed by dual antiplatelet therapy is associated with early neurological improvement and a higher probability of favorable 90-day functional outcome in patients with acute anterior-circulation small-artery occlusion ischemic stroke. The END and safety findings require confirmation through larger prospective studies.

Objective To identify drug-related problems （DRPs） in community stroke patients in Huairou District， Beijing， using the Pharmaceutical Care Network Europe （PCNE） classification system （version 9.1）， and to analyze the influencing factors of DRPs. Methods Community patients with stroke from July 2022 to December 2024 were enrolled. DRPs were identified using the PCNE classification system， and the influencing factors were analyzed. The PCNE classification system was used to identify DRPs， analyze their medication status and influencing factors， and examine the classification of drugs associated with DRPs. Results A total of 415 stroke patients were included. Among them， 218 patients （52.53%） experienced 400 DRP episodes. Logistic regression analysis revealed that drinking alcohol （OR=2.483，95%CI：1.364-4.522）， diabetes （OR=1.847，95%CI：1.061-3.218），medication adherence （OR=24.954，95%CI：14.246-43.710）， anxiety and depression （OR=2.157，95%CI：1.064-4.373）， and daily fluid intake （OR=0.468，95%CI：0.274-0.799） were independent risk factors for DRPs. Conclusion The medication status of Huairou District， Beijing community stroke patients is not ideal. Alcohol consumption， diabetes， medication adherence， anxiety/depression， and daily fluid intake are important influencing factors for DRPs and should be prioritized to reduce their occurrence.

Objective To explore the clinical effect of doxycycline combined with methylprednisolone in the treatment of children with refractory Mycoplasma pneumoniae pneumonia （RMPP）. Methods A retrospective analysis was conducted on children with RMPP who were diagnosed with RMPP admitted to the Department of Pediatrics， Beijing Luhe Hospital， Capital Medical University from January 2023 to June 2024. The children were divided into the observation group and the control group according to their treatment regimens. The control group was treated with azithromycin combined with methylprednisolone， while the observation group was treated with doxycycline combined with methylprednisolone. The clinical efficacy， symptom improvement time， and adverse reaction incidence of the two groups of children were compared. Results A total of 342 children were enrolled， with 171 in the observation group and 171 in the control group. The clinical effective rate of the observation group was 98.25%， which was higher than that of the control group （80.12%） （P<0.05）. The duration of time to fever resolution in the observation group was （4.15±1.26） d， the disappearance of cough was （8.11±2.18） days， the disappearance time of pulmonary rales was （13.47±3.39） days， and the recovery time of pulmonary lesions on chest CT was （15.36±4.18） days， all of which were shorter than those of the control group （6.16±1.84） days， （11.90±2.35） days， （16.91±3.82） days， and （19.00±4.25） days （P<0.05）. The total incidence of adverse reactions in the observation group was 4.09%， which was lower than that of the control group （13.45%） （P<0.05）. Conclusion Compared with azithromycin combined with methylprednisolone， doxycycline combined with methylprednisolone can improve the clinical efficacy of pediatric RMPP， accelerate the recovery process of the children， and reduce adverse reactions.

Objective To investigate the effects of penpulimab combined with chemotherapy on the expression of immune activation markers and ferroptosis-related molecules in metastatic non-small cell lung cancer （NSCLC） tissues， and to analyze their potential immuno-metabolic correlations. Methods Patients with stage IV metastatic NSCLC were randomized into the control group （nab-paclitaxel + cisplatin） and the observation group （penpulimab plus nab-paclitaxel + cisplatin）， both receiving six treatment cycles. Tumor tissue samples were collected pre-and post-treatment. Immunohistochemistry （IHC） was employed to detect the expression of programmed cell death protein-1 （PD-1）， major histocompatibility complex class I （MHC-I）， CD8⁺ T cells， interferon-gamma receptors 1/2 （IFNGR1/2）， Janus kinases 1/2 （JAK1/2）， signal transducer and activator of transcription 1 （STAT1）， solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， arachidonate 15-lipoxygenase （ALOX15）， and Ki-67. Results A total of 120 patients were enrolled （n=60 per group）. Immune profile analysis revealed that the observation group exhibited significant up-regulation of MHC-I （7.90±1.31 vs. 4.39±0.81， P<0.001）， increased CD8⁺ T-cell infiltration， and elevated serum IFN-γ levels （16.39±3.11 pg/mL vs. 8.94±1.79 pg/mL， P<0.001），compared with the control group. Furthermore， the expression levels of molecules in the IFNGR/JAK/STAT1 signaling axis were significantly higher in the observation group （all P<0.001）. Analysis of ferroptosis-related indicators revealed that the expression of SLC7A11 ［（3.88±0.90） vs. （6.55±1.01）］ and GPX4 ［（2.11±0.51） vs. （3.46±0.66）］ was significantly suppressed in the observation group compared with the control group. This suppression was accompanied by elevated reactive oxygen species （ROS） levels ［（5210.80±383.06） vs. （3894.46±175.80）］ and increased ALOX15 expression ［（8.15±2.18） vs. （3.80±1.31）］. Furthermore， Ki-67 expression in the observation group was markedly lower than that in the control group ［（4.81±0.91） vs. （6.97±0.98）］. Conclusion In metastatic NSCLC， immune checkpoint inhibitor therapy induces significant alterations in the tumor immune microenvironment， accompanied by synchronized changes in the expression profiles of ferroptosis-related molecules. This state of immune activation may be mechanistically linked to an increased susceptibility of tumor cells to ferroptosis and a concomitant reduction in proliferative activity.

Objective To clarify the functional requirements of voice interaction robots for pharmaceutical clinics， and provide evidence for the development of intelligent pharmaceutical assistants. Methods A self-designed online questionnaire was distributed to pharmacists working in pharmaceutical clinics of national tertiary medical institutions. The content covered the basic in formation of the pharmacy outpatient pharinacists， their current working conditions and the assessment of their demand for voice interaction rabots. Results A total of 294 valid responses were collected. The respondents were predominantly aged 36-45 （53.74%）， with 10-20 years of work experience （46.26%）， and holding intermediate professional titles （43.79%）. In terms of the current work situation adjustments， chronic disease medication （34.32%） and drug-drug interaction screening （29.59%） were the most time-consuming consultation types. Major communication challenges included incomplete patient medication history （78.7%） and insufficient disease descriptions （71.6%）. Structured entry of medication records （94.56%） and rapid drug information query （90.48%） were identified as core functional requirements. Real-time access to authoritative drug information （e.g.， package inserts and guidelines） ranked highest with a mean composite score of 4.24. In terms of human-machine collaboration， 92.86% of pharmacists preferred the “voice robot preliminary screening followed by pharmacist review”， model， and all emphasized the need to retain manual override functions. Conclusion Voice interaction robots for pharmaceutical clinics should prioritize automated medication record entry， rapid drug information retrieval， and prescription risk alerting， adopting a “machine-assisted， pharmacist-led” collaborative model.

Objective To conduct a comprehensive clinical evaluation of five marketed influenza virus RNA polymerase inhibitors in China based on the QuickGuideline for Drug Evaluation and Selection in Chinese Medical Institutions （third Edition）. Methods Five drugs approved for marketing in China by December 31， 2025 were included， namely baloxavir marboxil， suraxavir marboxil， sebaloxavir marboxil， onradivir， and pixavir marboxil. A systematic search was performed in Chinese and English databases， combined with drug package inserts， clinical guidelines， and economic data. Quantitative scoring and comparative analysis were carried out across five dimensions： effectiveness， safety， pharmaceutical characteristics， economy， and other attributes. Results All five drugs effectively alleviated clinical symptoms and shortened viral clearance time in patients with non-severe influenza， but showed significant differences in indications， applicability in special populations， pharmaceutical properties， economy， and accessibility. The overall scores in descending order were： baloxavir marboxil 75.6， onradivir 73.2， suraxavir marboxil 67.5， sebaloxavir marboxil 63.9， and pixavir marboxil 62.3. Baloxavir marboxil had prominent advantages in indication coverage， guideline recommendation level， and applicability in special populations； onradivir performed excellently in pharmaceutical characteristics and economy. Conclusion All five influenza virus RNA polymerase inhibitors demonstrate certain clinical value， with distinct advantages across different dimensions. Medical institutions may consider patient population characteristics， medical insurance affordability， and in-hospital medication management needs when making hierarchical drug selection and promoting individualized rational use.

Objective To evaluate the cost-effectiveness of tafolecimab combined with statins in the treatment of hypercholesterolemia and provide evidence-based support for clinical treatment decisions and the optimal allocation of medical resources. Methods From the perspective of the Chinese healthcare system， a Markov model with five mutually exclusive health states was constructed to simulate the disease progression of patients with hypercholesterolemia. The model cycle was one year， and the study period was 20 years. Rate parameters， cost parameters， and effect parameters were derived from the CREDIT series of studies， statistical yearbooks， and published literature. The effect was expressed in quality-adjusted life years （QALYs）. The incremental cost-effectiveness ratio （ICER） was used to evaluate the cost-effectiveness of tafolecimab. Results The base-case analysis showed that the total cost of the tafolecimab group was 195 627.3 yuan， and the total effect was 17.95 QALYs； the total cost of the conventional medication group was 134，173.5 yuan， and the total effect was 16.36 QALYs. Compared with the conventional medication group， the ICER of the tafolecimab group was 38 650 yuan/QALY. With a willingness-to-pay （WTP） threshold of two times the per capita GDP of China in 2022， which is 171 396 yuan/QALY， tafolecimab demonstrated economic advantages. One-way sensitivity analysis indicated that drug treatment cost in the tafolecimab group was a key influencing factor. The probabilistic sensitivity analysis results showed that the probability of tafolecimab being cost-effective was as high as 100%，under the current WTP threshold. Conclusion Under the current medical price system and in the context of statins treatment， the combination of tafolecimab with statins has a clear cost-effectiveness advantage and can provide a better treatment option for patients with hypercholesterolemia in China.

Objective To conduct a comprehensive clinical assessment of efgartigimod alfa injection and provide evidence to inform clinical decision making and rational use. Methods Based on the dimensions and indicators recommended in the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs， we used literature review and questionnaire survey methods to evaluate the effectiveness， safety， cost-effectiveness， innovation， suitability， and accessibility of efgartigimod alfa injection in generalized myasthenia gravis （gMG） using qualitative and quantitative approaches. Results Of 514 records identified， 7 studies were included. Efgartigimod alfa significantly improved Myasthenia Gravis Activities of Daily Living （MG-ADL）， Quantitative Myasthenia Gravis （QMG）， and 15-item Myasthenia Gravis Quality of Life （MG-QOL15） scores， and increased the MG-ADL response. The incidence of adverse events was comparable with that of placebo and other biologics. The estimated lifetime drug cost of efgartigimod alfa was RMB 3，106，504； compared with rituximab and conventional treatment， it showed no cost-effectiveness advantage. As the first neonatal Fc receptor （FcRn） antagonist approved worldwide， efgartigimod alfa offers a differentiated targeted strategy for gMG and other IgG-mediated autoimmune diseases， representing substantial therapeutic innovation. Its flexible dosing regimen supports individualised treatment， and its cycle-based administration with a lower incidence of systemic adverse events may improve adherence. Although efgartigimod alfa has been included in China’s national medical insurance drug list， its uptake in healthcare institutions remains limited and affordability is suboptimal. Conclusion Efgartigimod alfa demonstrates advantages in efficacy， safety， suitability， and innovation.

Objective To investigate the basic status of the ceftazidime-avibactam among hospitalized patients in a traditional Chinese medicine hospital， and to provide a basis for rational clinical application. Methods Medical records of hospitalized patients who used ceftazidime-avibactam in the traditional Chinese medicine hospital from July 2024 to April 2025 were collected， population characteristics， departments， medication regimen， pathogen examination， duration of use and combination therapy were statistically analyzed. Results A total of 85 hospitalized patients were treated with ceftazidime-avibactam， including 50 males and 35 females， aged 52-99 years old. The department of general surgery had the highest number of cases. The pathogen detection rate before using ceftazidime-avibactam was 83.53%， and the detected bacteria was mainly Klebsiella pneumoniae （ESBL+）. 72.94% of patients were administered according to the dosage of 2.5 g per 8 hours as stated in the drug instructions. The most commonly used antibiotics in combination with ceftazidime-avibactam were metronidazole， vancomycin， and tigecycline. 71 patients （83.53%） had inappropriate use of ceftazidime-avibactam， among them， the proportion of unreasonable indications was the highest （41.18%）， followed by no special level consultation before medication （21.57%） and prolonged treatment course （15.69%）. Conclusion The clinical rationality of the use of cefotaxime-avibactam needs to be improved in this hospital. Strict control of indications is required during treatment， and a special level consultation process should be implemented to standardize the course of treatment， sample submission， and indications for combination therapy， so as to promote the rational use of antibiotics.

Q fever is a natural focal disease caused by Coxiella burnetii， which is a zoonotic disease that can lead to severe complications such as endocarditis， vasculitis， and liver damage. Sporadic acute Q fever has a low incidence and presents with nonspecific clinical symptoms， posing challenges for diagnosis and treatment. We report a case of a patient with fever of unknown origin who improve after receiving cefaclor extended-release tablets for 3 days. The patient was diagnosed with Coxiella burnetii infection via metagenomic next-generation sequencing （mNGS）， and the treatment regimen was adjusted to minocycline combined with moxifloxacin. Following the adjustment， the patient's clinical symptoms improved rapidly. Two weeks after starting the anti-infective therapy， blood mNGS was repeated and revealed that Coxiella burnetii was no longer detectable， suggesting that this regimen may eliminate Coxiella burnetii at the nucleic acid level.

This article reports a case of a 47-year-old male with acute-on-chronic liver failure who developed a delayed-type hypersensitivity reaction during treatment with intramuscular vitamin K₁ （10 mg/day） to improve coagulation. On day 10 of treatment， erythema appeared at the injection site， followed by a rapid spread of the rash to the abdomen and limbs， progressing into diffuse maculopapular rash， edematous erythema with epidermal exudation， and hemorrhagic lesions. After discontinuing vitamin K₁， treatment with antihistamines and topical steroids was ineffective. Subsequently， a 3-day course of intravenous methylprednisolone combined with gamma globulin led to gradual resolution of the rash， with most lesions healing by day 32. A Naranjo score of 7 indicated a "probable" association with vitamin K₁.