As a new transdermal drug delivery system, microneedles can significantly improve skin permeability, enhance drug transdermal delivery, and demonstrate unique advantages in breaking stratum corneum barrier of skin. This feature enables microneedles to demonstrate enormous potential in delivering biotechnology drugs. The traditional delivery method for biotechnology drugs is mainly injection, which brings problems such as pain and skin redness to patients, leading to poor patient compliance. In addition, the production, transportation, and storage of biotechnology drugs require strict low-temperature conditions to maintain their activity and increase cost output. Microneedles, by contrast, have many benefits, providing new avenues and solutions for biomolecular delivery. Accordingly, this review introduced the microneedle drug delivery system for delivery biotechnology drugs, and summarized the research progress of microneedle systems in biotechnology drugs.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Humans ; Lymphoma, T-Cell, Cutaneous/complications* ; Neuroglia ; Pruritus/pathology* ; Skin Neoplasms/complications* ; Spinal Cord/pathology* ; Sympathetic Nervous System

Purpose: This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. Materials and Methods: Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS). Results: Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05). Conclusion Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.

Background: Periprosthetic infection after total knee arthroplasty is a challenging problem, and physicians should identify risk factors to decrease recurrence. However, risk factors for reinfection with two-stage reimplantation have not yet been well established. The purpose of this study was to assess treatment outcomes of subsequent twostage knee reimplantation and identify risk factors for uncontrolled periprosthetic knee joint infections. Methods: We retrospectively reviewed 70 knees diagnosed with a periprosthetic knee joint infection treated with two-stage reimplantation between September 2011 and October 2016 at our institution. Patients in the controlled infection group (group C) required no further medication or surgical treatment within 2 years after reimplantation.Patients in the uncontrolled infection group (group U) displayed symptoms of active infection after resection arthroplasty or were reinfected after two-stage reimplantation. We compared group C and group U, and analyzed potential risk factors for uncontrolled prosthetic joint infection (PJI). Results: Of 70 knees included in this analysis, 53 (75.7%) were clinically deemed free from infection at the latest follow-up. The remaining 17 knees (24.3%) required additional surgical procedures after two-stage reimplantation.Demographics were not statistically significantly different between the two groups. Wound complications were statistically more frequent in group U (p = 0.030). Pre-reimplantation C-reactive protein (CRP) was statistically different between groups C and U (0.44 and 1.70, respectively, (p = 0.025). Among the cultured microorganisms, fungus species were statistically more frequently detected in group U compared with group C ((p = 0.031). Conclusions The reinfection rate of our two-stage reimplantation protocol was 24.3% in the included cases.Wound complications, higher pre-reimplantation CRP levels, and fungus species were statistically more common in group U compared with group C. Our findings will help in counseling patients and physicians to understand that additional caution may be required when treating PJI if the aforementioned risk factors are present.Level of evidence: IV, case series.

In this experiment, the decoction process of famous classical formula Xiebai San was determined by optimizing the particle size of "Cuo san" and investigating the decoction process parameters, such as boiling container, water volume and duration. Xiebai San was taken as an example to explore the study method of the "Cuo san" in the famous classical formulas. The specific chromatogram of Xiebai San and the determination method of glycyrrhizin and glycyrrhizic acid in Xiebai San were established. Different particle sizes of "Cuo san" and decoction parameters were optimized based on the similarity of specific chromatogram, the specific chromatogram's peak area, the content of glycyrrhizin, the content of glycyrrhizic acid and extract yield rate.The particle size of Xiebai San powder was determined to be 2.00-4.75 mm(by four-mesh sieves). The decoction process was determined as follows: put the prescription amount into a ceramic pot, add 420 mL of water, and boil and simmer until the volume is 300 mL.The similarity of specific chromatogram was above 0.9, the specific chromatogram's peak area was larger, the content of glycyrrhizin was 0.12%, the content of glycyrrhizic acid was 0.21%,and the extract yield rate was 15.05%. The finally determined particle size of "Cuo san" can better represent the quality of Xiebai San, and is easy to prepare and suitable for industrial production.This experimental research method can comprehensively investigate the quality of Xiebai San as a whole, the content of active ingredients, and the situation of extract yield.It is a more comprehensive and objective evaluation method, and can provide experimental basis and reference for the study of other "Cuo san" famous classical formulas.
Drugs, Chinese Herbal/chemistry* ; Glycyrrhizic Acid/analysis* ; Particle Size ; Powders ; Technology, Pharmaceutical

Distal clavicle fractures are less common than mid-shaft fractures in adults and there is no consensus on the best classification system or the ideal treatment approach considering that high nonunion rates have been reported. Although there are numerous treatment options for distal clavicle fractures, a gold standard treatment has not yet been established. Each surgical technique has its pros and cons. In this review article, we provide an overview of classification systems and treatment methods for distal clavicle fractures.

To establish a determination method for the contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid of Baimai Ointment,and investigate the percutaneous permeability of Baimai Ointment and the effects of two kinds of penetration enhancers on percutaneous absorption of three components. The contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid were determined by high pressure liquid chromatography( HPLC). The vertical modified Franz diffusion cell was used to perform a transdermal experiment in vitro with the abdominal skin of mice( treated and untreated). The transdermal receptor liquid was preferably used to investigate the transdermal absorption rule of the Baimai Ointment and the effect of the penetration enhancer. The results showed that the comprehensive solubility of PEG-ET-NS( 3 ∶3 ∶4) was best among three types of receptor liquid PG-ET-NS( 3 ∶3 ∶4),PEG-ET-NS( 3 ∶3 ∶4),ET-NS( 3 ∶7). PEG-ET-NS was used as the receptor liquid for in vitro transdermal experiments. The cumulative permeation area of ammonium glycyrrhetate,nardosinone and curcumin within 24 h was 5. 73,18. 99,0. 38 μg·cm~(-2)respectively. Taking QEFand ER as comprehensive evaluation indicators of permeation performance,the comprehensive penetration-promoting performance of ammonium glycyrrhizinate: 3% PEG 400-ethanol-normal saline ≈ 1. 19 times( 3%azone) = 1. 94 times( blank); comprehensive penetration-promoting performance of nardosinone: 3% PEG 400-ethanol-normal saline≈1. 28 times( 3% azone) = 1. 37 times( blank); the comprehensive penetration performance of curcumin: 3% PEG 400-ethanol-normal saline≈1. 77 times( 3% azone) ≈3. 42 times( blank). The comprehensive penetration enhancement properties of the two penetration enhancers were as follows: 3% PEG 400-ethanol-normal saline>3%azone>blank. The transdermal absorption curve of ammonium glycyrrhetate,nardosinone and curcumin in Baimai Ointment were consistent with the zero-order equation,indicating that the transdermal absorption process was irrelevant to the concentration of three components,and its was a diffusion process. This experiment provides reference for the study of ointment transdermal preparations.
Administration, Cutaneous ; Animals ; Mice ; Ointments ; pharmacokinetics ; Permeability ; Skin ; Skin Absorption

Objective: To study the effective substance foundation of Ephedrae Herba and explore its mechanism, in order to further enrich the theory of drug resistance of Ephedrae Herba.Method: In this experiment, a compound model was used to establish rat model of Harmful Fluid Retention in upper Jiao. The Rats were randomly divided into model group, captopril group (4.38 mg·kg^-1), Ephedrae Herba decoction group(468 mg·kg^-1), polysaccharide group (265.36 mg·kg^-1), volatile oil group (2.34 mg·kg^-1), alkaloid group(40.71 mg·kg^-1) and phenolic acid group (210.60 mg·kg^-1), and normal group (10 mL·kg^-1). The normal group and the model group were given the same volume of normal saline for four weeks. The 24 h urine volume of rats was collected by metabolic cage method. The changes of heart and lung tissue morphology were observed under light microscope. The heart index, lung index, left ventricular ejection fraction(LVEF), left ventricular short axis shortening rate(LVFS) and pulmonary permeability index, number(LPI), lung dry-wet ratio(W/D), creatine kinase isoenzyme(CK-MB), angiotensin Ⅱ(Ang Ⅱ), aldosterone(ALD), cardiac aquaporin 1(AQP1), lung AQP1, aquaporin-3(AQP3) and kidney AQP1, aquaporin-2(AQP2), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) change were detected.Result: Compared with the normal group, heart and lungs of the model group were significantly damaged. The amount of 24 h urine, LVEF, LVFS of model rats were significantly reduced(P<0.01); whereas heart index, lung index, CK-MB, LPI, Ang Ⅱ, W/D, ALD, IL-6 and TNF-α were significantly increased(P<0.05,P<0.01), and the model of Harmful Fluid Retention in the Upper Jiaowas established successfully. The amount of 24 h urine, LVEF, LVFS, IL-6 and TNF-α were significantly increased (P<0.05, P<0.01) in the alkaloid group, and the heart index, the lung index, CK-MB, LPI, Ang Ⅱ, W/D, ALD, IL-6 and TNF-α were significantly reduced (P<0.05, P<0.01). And the Alkaloid group can alleviate the heart and lung pathology in the Rats Model of Harmful Fluid Retention in the Upper Jiao.Conclusion: Alkaloid components "Wen" and "Xin" are the effective substance basis of its action. The mechanism may be related to the inhibition of renin angiotensin aldosterone system (RAAS) and the anti-inflammatory effect.