OBJECTIVE To comprehensively analyze the effectiveness， safety and economic value of carfilzomib in the treatment of multiple myeloma （MM）， and provide evidence-based guidance for clinical rational drug use. METHODS A systematic search was performed in PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang， VIP， and relevant health technology assessment （HTA） websites， from database inception to December 31， 2024. Two researchers independently screened studies based on predefined inclusion and exclusion criteria， extracted data， and assessed study quality. Descriptive statistical analyses were conducted. RESULTS A total of 21 studies were included， comprising 7 systematic reviews/meta-analyses， 5 clinical trials， 5 pharmacoeconomic studies， and 4 HTA reports. Effectiveness analysis indicated that， compared with control groups， carfilzomib significantly improved overall response rate and clinical benefit rate （ P ＜0.05）， prolonged progression-free survival， and enhanced patient’s quality of life （ P ＜0.05）， while its impact on overall survival remains to be further confirmed. Safety analysis showed there was no significant difference in the risk of peripheral neuropathy between carfilzomib and controls， while the risks of cardiotoxicity and hypertension were significantly increased （ P ＜0.05）. Economic analysis suggested that carfilzomib regimens demonstrated certain cost-effectiveness in second-line treatment in the U.S. and some European countries. However， its economic value was influenced by drug price， dosing regimen， and regional differences， and it may lack a cost advantage in some countries or in third-line treatment. CONCLUSIONS Carfilzomib shows definite efficacy and generally acceptable safety in the treatment of MM， but cardiotoxicity and hypertension risks require careful monitoring. Given its high treatment cost， pharmacoeconomic studies in the Chinese population are urgently needed.

Objective: To analyze the intervention effects of moderate to vigorous classroom physical exercise on psychological sub health among Uyghur junior high school students, providing reference for mental health promotion and intervention in the ethnic group. Methods: From April to July 2022, 647 eighth grade Uighur junior high school students from two middle schools in the Kashgar Prefecture, Xinjiang, were selected using a random cluster digital sampling method. They were randomly assigned to a control group ( n =326) and an intervention group ( n =321). While adhering to the regular curriculum, the intervention group additionally received 12 week, 36 session (every Monday, Wednesday, and Friday afternoon) moderate to vigorous classroom physical exercise intervention (45 minutes per session, including warm up, main exercises, and cool down activities). Self administered psychological sub health was completed through Brief Instrument on Psychological Health of Youths before and after intervention, and the data were analyzed using covariance analysis. Results: Before intervention, there were no statistically significant differences between the control and intervention groups in the total scores for psychological sub health or in the scores for the three dimensions including emotional problems, conduct problems, and social adaptation difficulties ( t =0.76, 0.40, 0.01, 0.94 , all P >0.05). After intervention, the scores of the intervention group s junior high school students on the emotional problems, conduct problems, and social adaptation difficulties dimensions decreased by 0.50, 0.28, and 0.18, respectively, compared with the control group, and all differences were statistically significant ( t =3.35, 3.36, 2.07, all P <0.05). The main effect of the psychological sub health category was statistically significant ( F =60.66, P <0.01, partial η 2=0.09). Compared with the control group, the psychological sub health scores of junior high school students in the intervention group decreased by 0.96 ( t =3.42, P < 0.05 ). Conclusion The 12 week moderate to vigorous classroom physical exercise intervention has a positive effect on the psychological sub health of Uyghur junior high school students.

Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.

As human deep space exploration enters a practical phase, ensuring astronaut health and safety has become a critical determinant of mission success. The cerebrovascular system, essential for maintaining brain function, is highly sensitive to environmental changes. Cerebrovascular diseases represent one of the characteristic adverse effects of deep space conditions such as microgravity and high-energy radiation, and have emerged as a frontier challenge in space medicine. Based on experiences from manned space missions, major research challenges persist, particularly the lack of experimental data specific to the lunar environment and the unclear threshold for low-dose radiation-induced injury. Elucidating the mechanisms and multifactorial interactions by which deep space environments impact cerebrovascular structure and function, and summarizing the key risk factors, pathological processes, and recent advances in monitoring and early-warning technologies for cerebrovascular diseases in lunar astronauts, and of crucial importance. A comprehensive understanding of the interplay between deep space environmental stressors and cerebrovascular injury, as well as the development of personalized prevention and intervention strategies, will provide both theoretical and practical foundations for safeguarding cerebrovascular health in future Chinese deep space missions, while promoting progress in related biomedical research, technological innovation, and international collaboration.
Humans ; Astronauts ; Cerebrovascular Disorders/etiology* ; Space Flight ; Weightlessness/adverse effects* ; Risk Factors ; Moon

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

OBJECTIVES: To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS: A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals ; Female ; Cisplatin/pharmacology* ; Ovarian Neoplasms/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred BALB C ; Mice ; Rats ; Xenograft Model Antitumor Assays ; Humans ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology*

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

Nanocarrier-based drug delivery systems (nDDSs) present significant opportunities for improving disease treatment, offering advantages in drug encapsulation, solubilization, stability enhancement, and optimized pharmacokinetics and biodistribution. nDDSs, comprising lipid, polymeric, protein, and inorganic nanovehicles, can be guided by or respond to biological cues for precise disease treatment and management. Equipping nanocarriers with tissue/cell-targeted ligands enables effective navigation in complex environments, while functionalization with stimuli-responsive moieties facilitates site-specific controlled release. These strategies enhance drug delivery efficiency, augment therapeutic efficacy, and reduce side effects. This article reviews recent strategies and ongoing advancements in nDDSs for targeted drug delivery and controlled release, examining lesion-targeted nanomedicines through surface modification with small molecules, peptides, antibodies, carbohydrates, or cell membranes, and controlled-release nanocarriers responding to endogenous signals such as pH, redox conditions, enzymes, or external triggers like light, temperature, and magnetism. The article also discusses perspectives on future developments.
Humans ; Drug Carriers/chemistry* ; Drug Delivery Systems/methods* ; Delayed-Action Preparations/chemistry* ; Nanoparticles/chemistry* ; Animals ; Drug Liberation ; Nanomedicine