Pure drug nanomedicines (PDNs) encompass active pharmaceutical ingredients (APIs), including macromolecules, biological compounds, and functional components. They overcome research barriers and conversion thresholds associated with nanocarriers, offering advantages such as high drug loading capacity, synergistic treatment effects, and environmentally friendly production methods. This review provides a comprehensive overview of the latest advancements in PDNs, focusing on their essential components, design theories, and manufacturing techniques. The physicochemical properties and in vivo behaviors of PDNs are thoroughly analyzed to gain an in-depth understanding of their systematic characteristics. The review introduces currently approved PDN products and further explores the opportunities and challenges in expanding their depth and breadth of application. Drug nanocrystals, drug-drug cocrystals (DDCs), antibody-drug conjugates (ADCs), and nanobodies represent the successful commercialization and widespread utilization of PDNs across various disease domains. Self-assembled pure drug nanoparticles (SAPDNPs), a next-generation product, still require extensive translational research. Challenges persist in transitioning from laboratory-scale production to mass manufacturing and overcoming the conversion threshold from laboratory findings to clinical applications.
Nanomedicine ; Humans ; Nanoparticles/chemistry* ; Pharmaceutical Preparations/chemistry* ; Animals ; Drug Carriers/chemistry*

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

OBJECTIVE: To investigate the variability of bone metabolism levels among different populations and its association with knee osteoarthritis (KOA) pain. METHODS: A total of 50 people (control group) who participated in physical examination from January 2023 to June 2023 were selected, including 26 males and 24 females, wtih a mean aged of (52.14±9.04) years old ranging 41 to 65 years old. The other 50 patients with knee osteoarthritis(case group) who attended the outpatient clinic of the Orthopedics and Traumatology Department in the same time period, including 19 males and 31 females, with a mean age of (53.60±7.76) years old ranging 40 to 65 years. The two groups of Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) and bone metabolism markers, such as 25-hydroxy-cholecalciferol[25(OH)D], β-isomerized typeⅠcollagen C-telopeptide breakdown products (β-CTX), total typeⅠprocollagen N-terminal propeptide (t-PINP), osteocalcin (OC), parathormone (PTH) levels were compared. Pearson correlation analysis was used to compare the correlation between two groups of bone metabolism related markers and WOMAC. RESULTS: The WOMAC score of the case group (39.90±2.34) was higher than that of the control group (3.60±0.57), with significant difference (P<0.05). There was no significant difference between the two groups of 25 (OH)D, β-CTX and PTH (P>0.05). The t-PINP and OC of the case group were (62.90±52.40) and (19.88±10.15) ng·ml-1, respectively, and those of the control group were (38.86±10.82) and (14.90±3.62) ng·ml^-1, respectively;the t-PINP and OC of the case group were higher than those of the control group, with significant difference (P<0.05). Pearson correlation analysis showed that t-PINP was positively correlated with WOMAC pain score in the case group (r²=0.045, P<0.01). CONCLUSION Bone metabolism levels in the serum of patients with knee osteoarthritis are different from those of healthy people, and the difference between OC and t-PINP is the most obvious, and the concentration of t-PINP levels is positively correlated with pain symptoms in patients with KOA. However, the specific mechanism of correlation between the bone metabolism levels of patients with KOA and their pain symptoms needs to be further elucidated by basic experimental research as well as by enlarging the samples.
Humans ; Female ; Male ; Middle Aged ; Osteoarthritis, Knee/metabolism* ; Aged ; Adult ; Bone and Bones/metabolism* ; Pain/etiology* ; Biomarkers/metabolism*

Objective·To investigate the spatial epigenetic characteristics of spontaneous colon tumors in Apcmin/+mice.Methods·A spatial assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)technology platform was established using an eight-month-old male Apcmin/+mouse model with spontaneous colon tumors.One tumor from a mouse was harvested and embedded in OCT compound for serial cryosectioning;one tissue section was stained with hematoxylin-eosin(H-E)to observe its histological characteristics,while an adjacent section was processed using spatial ATAC-seq technology to generate spatially resolved DNA libraries,followed by sequencing to obtain spatial chromatin accessibility data.Another tumor from the same mouse was digested into a single-cell suspension,in which viable single cells were sorted by flow cytometry and processed for single-cell RNA sequencing.The results were integrated with spatial chromatin accessibility data to jointly analyze the epigenetic characteristics of the colon tumor microenvironment.Results·A stable spatial ATAC-seq platform was successfully established,dividing the tumor into malignant,non-malignant,and malignant-non-malignant boundary regions.Transcription factors enriched in malignant regions included NK2 homeobox 5(NKX2-5)and transcription factor 3(TCF3).Analysis of transcription factor enrichment in the 3 regions revealed two distinct expression trends:one showing a gradual decrease from malignant to boundary to non-malignant regions,and the other exhibiting high expression in malignant and boundary regions but low expression in non-malignant regions.Gene analysis across regions revealed significant upregulation of hypoxia response,transforming growth factor(TGF),and Kirsten rat sarcoma viral oncogene homolog(KRAS)signaling pathways in malignant regions,with cell cycle-related functions markedly enhanced.Analysis of cell-cell interactions in the tumor microenvironment revealed significant differences in interaction strength:strong interactions within non-malignant regions,moderate interactions between boundary and non-malignant regions,and weak interactions between malignant and boundary regions as well as between malignant and non-malignant regions.Conclusion·Colon tumors in Apcmin/+mice exhibit high spatial heterogeneity;malignant regions were enriched with transcription factors including TCF3,and cell interactions between malignant regions and boundary/non-malignant regions were relatively weak.

Chiropractic therapy is a therapeutic approach for regulating the spine and is widely employed in clinical practice for multiple disorders, including constipation. The theory of "bone strengthening and tendon softening" originated from Huang Di Nei Jing, holding that bones maintain normal anatomical forms and relative positional relationships, and tendons are supple and free from damage. Only when the structures and functions of both are normal can the human body sustain normal physiological activities. In accordance with this theory, clinical treatment mainly aims at adjusting the relationship between tendons and bones and restoring the balance between them to address diseases. Based on the theory of "bone strengthening and tendon softening" and taking the essence of "tendons" as the starting point, this article explored the pathogenic mechanism of outlet obstructive constipation and the clinical application of chiropractic therapy in the treatment of outlet obstructive constipation. Pathological changes of the musculotendinous meridians and abnormal spinal structures are significant pathogenic factors for outlet obstructive constipation. Therefore, in clinical practice, spinal techniques such as guided manipulation, massage, and reconstructive techniques can be used to soften muscles, correct bones, and regulate intestinal stagnation.

Objective Based on the assumption of spatial heterogeneity,the distribution pattern and risk characteristics of health poverty in middle-aged and elderly people with chronic diseases are described from the perspective of spatial differentiation.In order to providing a theoretical basis for the optimization of subsequent poverty reduction policies and a model policy for other countries.Methods It used factor detector and interaction detector to capture the role of single-factor and multi-factor interactions on the spatial differentiation of health poverty,and risk detectors were utilized to explore the high-risk factors in risky areas Results The single factor explanation of medical assistance and health education activities is prominent,and the factors such as PM2.5,old-age dependency ratio and urban unemployment rate have strong interaction.Furthermore,it identified high-risk factor characteristics in areas at high risk of health poverty.Conclusion The spatial differentiation pattern of health poverty among the middle-aged and elderly chronic disease population in China is the result of the synergistic driving effect of multidimensional factors,and there is variability in the risk characteristics among regions.The government should establish a contextual optimization strategy and pay attention to the joint effect of multiple factors to establish a synergistic management system.

Objective·To investigate the spatial epigenetic characteristics of spontaneous colon tumors in Apcmin/+mice.Methods·A spatial assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)technology platform was established using an eight-month-old male Apcmin/+mouse model with spontaneous colon tumors.One tumor from a mouse was harvested and embedded in OCT compound for serial cryosectioning;one tissue section was stained with hematoxylin-eosin(H-E)to observe its histological characteristics,while an adjacent section was processed using spatial ATAC-seq technology to generate spatially resolved DNA libraries,followed by sequencing to obtain spatial chromatin accessibility data.Another tumor from the same mouse was digested into a single-cell suspension,in which viable single cells were sorted by flow cytometry and processed for single-cell RNA sequencing.The results were integrated with spatial chromatin accessibility data to jointly analyze the epigenetic characteristics of the colon tumor microenvironment.Results·A stable spatial ATAC-seq platform was successfully established,dividing the tumor into malignant,non-malignant,and malignant-non-malignant boundary regions.Transcription factors enriched in malignant regions included NK2 homeobox 5(NKX2-5)and transcription factor 3(TCF3).Analysis of transcription factor enrichment in the 3 regions revealed two distinct expression trends:one showing a gradual decrease from malignant to boundary to non-malignant regions,and the other exhibiting high expression in malignant and boundary regions but low expression in non-malignant regions.Gene analysis across regions revealed significant upregulation of hypoxia response,transforming growth factor(TGF),and Kirsten rat sarcoma viral oncogene homolog(KRAS)signaling pathways in malignant regions,with cell cycle-related functions markedly enhanced.Analysis of cell-cell interactions in the tumor microenvironment revealed significant differences in interaction strength:strong interactions within non-malignant regions,moderate interactions between boundary and non-malignant regions,and weak interactions between malignant and boundary regions as well as between malignant and non-malignant regions.Conclusion·Colon tumors in Apcmin/+mice exhibit high spatial heterogeneity;malignant regions were enriched with transcription factors including TCF3,and cell interactions between malignant regions and boundary/non-malignant regions were relatively weak.

Objective Based on the assumption of spatial heterogeneity,the distribution pattern and risk characteristics of health poverty in middle-aged and elderly people with chronic diseases are described from the perspective of spatial differentiation.In order to providing a theoretical basis for the optimization of subsequent poverty reduction policies and a model policy for other countries.Methods It used factor detector and interaction detector to capture the role of single-factor and multi-factor interactions on the spatial differentiation of health poverty,and risk detectors were utilized to explore the high-risk factors in risky areas Results The single factor explanation of medical assistance and health education activities is prominent,and the factors such as PM2.5,old-age dependency ratio and urban unemployment rate have strong interaction.Furthermore,it identified high-risk factor characteristics in areas at high risk of health poverty.Conclusion The spatial differentiation pattern of health poverty among the middle-aged and elderly chronic disease population in China is the result of the synergistic driving effect of multidimensional factors,and there is variability in the risk characteristics among regions.The government should establish a contextual optimization strategy and pay attention to the joint effect of multiple factors to establish a synergistic management system.

OBJECTIVE: To explore clinical effect of Zero-profile intervertebral fusion with cage-titanium plate in treating multilevel cervical spondylotic myelopathy. METHODS: From January 2016 to January 2020, 107 patients with multisegmental cervical spondylotic myelopathy treated by surgery were retrospectively analyzed and divided into Hybrid group and control group according to different surgical methods. There were 54 patients in Hybrid group, including 42 males and 12 females, aged from 33 to 77 years old with an average of (57.3±9.5) years old;20 patients with C₃-C₆, 27 patients with C₄-C₇ and 7 patients with C₃-C₇;Zero-profile intervertebral fusion with cage-titanium plate internal fixation was performed. There were 53 patients in control group, including 34 males and 19 females;aged from 36 to 79 years old with an average of (57.8±8.9) years old;17 patients with C₃-C₆, 27 patients with C₄-C₇, and 9 patients with C₃-C₇;titanium plate interbody fusion fixation was performed. Operation time, blood loss and complications between two groups were compared, visual analogue scale (VAS), Japanese Orthopedic Association (JOA) scores and neck disability index (NDI) were used to assess recovery of clinical symptoms;cervical lordosis (CL), cervical sagittal vertical axis (C-SVA), and T₁ slope (T₁S) were measured and compared to evaluate cervical sagittal plane parameters. RESULTS: All patients were followed up, Hybrid group was followed up for 24 to 64 months with an average of (31.7±18.4) months, and control group was followed up for 24 to 65 months with an average of (32.6±15.8) months. There was no significant difference in follow-up time between two groups (P>0.05). Operation time and blood loss in Hybrid group were less than those in control group (P<0.05). VAS, JOA score and NDI were significantly improved between two groups at the lastest follow-up (P<0.05). There were no significant difference in VAS, JOA and NDI scores between two groups before and after operation (P>0.05). CL in both two groups at 3 months and the latest follow-up after operation were significantly improved than those before operation (P<0.05), there were no significant difference between two groups in T1S and C-SVA before and after operation (P>0.05). Postoperative dysphagia occurred in 2 patients in Hybrid group and 9 patients in control group, and had statistically difference in the incidence of dysphagia between two groups (χ²=5.112, P=0.024). During the follow-up, there were no complications such as loosening, displacement or fracture of internal fixation between two groups. CONCLUSION Compared with titanium plate interbody fusion, Zero-profile intervertebral fusion combined with cage-titanium plate for the treatment of multilevel cervical spondylotic myelopathy could shorten surgical time and blood loss, reduce surgical trauma and postoperative swallowing difficulties, and is conducive to early and rapid recovery.
Humans ; Male ; Female ; Middle Aged ; Spinal Fusion/instrumentation* ; Bone Plates ; Titanium ; Aged ; Spondylosis/surgery* ; Adult ; Cervical Vertebrae/surgery* ; Retrospective Studies ; Spinal Cord Diseases/surgery*