OBJECTIVE To prepare the β -cyclodextrin （ β -CD） inclusion complex with volatile oil from Qianghuo qushi qingwen granules， and to characterize and quantitatively analyze the inclusion complex. METHODS The comprehensive scores calculated by inclusion rate and inclusion compound yield were used as indicators for screening the inclusion method. The single-factor experiments and Box-Behnken response surface experiments were used to op timize the inclusion conditions， with the above comprehensive score as response value， and taking the ratio of β -CD to volatile oil， inclusion temperature and inclusion time as indexes. The volatile oil inclusion complex of Qianghuo qushi qingwen granules was prepared according to the determined optimal process， followed by validation. Ultraviolet （UV）-visible spectroscopy， thin-layer chromatography （TLC）， and microscopic imaging were also performed. Ultra-high performance liquid chromatography was used to determine the contents of perillaldehyde， pogostone and atractylodin. RESULTS The saturation aqueous solution method was adopted. The optimal inclusion process conditions were as follows： the ratio of β -CD to volatile oil was 7.5∶1， the inclusion temperature was 40 ℃， and the inclusion time was 2.2 h. In three verification experiments， the average inclusion rate was 72.32%， the average yield of inclusion compound was 74.45%， the average comprehensive score was 72.96 points， and the relative error with the predicted value （74.15 points） of the model was 1.61%. UV-visible spectroscopy， TLC and microscopic imaging showed that β -CD and volatile oil successfully formed a new inclusion complex. The average contents of perillaldehyde， pogostone and atractylodin were 4.498 2， 0.814 9， 0.905 7 mg/g， respectively， with RSDs of 0.31%， 0.56% and 0.63% （ n ＝3）. CONCLUSIONS A stable and feasible preparation process of the volatile oil inclusion complex of Qianghuo qushi qingwen granules is successfully established.

Rare neurological diseases account for over one-third of the diseases included in the first and second batches of China′s Rare Disease Catalogue. They are generally characterized by high disability rates, heavy care burdens, and prominent unmet clinical treatment needs. In recent years, China has been continuously improving medication accessibility for patients with rare neurological diseases by optimizing the review and approval pathways for rare disease drugs, implementing dynamic medical insurance access, and providing policy support for scientific research. However, challenges remain, including weak independent research and development (R&D) capacity and insufficient translation of high-quality research achievements into clinical practice. Based on the supply gap of clinical treatment resources for rare neurological diseases in China and the overall landscape of global R&D pipelines, this paper summarizes and discusses the current status, characteristics, and future directions of drug development for rare neurological diseases in China.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

As an important strategy in antiviral drug development, nucleoside analogs (NAs) have attracted considerable attention due to their unique mechanisms of action and favorable safety profile. This review systematically summarizes recent advances in the mechanisms of action of NAs, focusing on the following four aspects: (1) Targeting viral polymerases, inhibiting viral replication through mechanisms such as non-absolute termination, delayed chain termination and induction of viral RNA mutations in addition to classical chain termination, which has been newly discovered; (2) Regulating RNA methylation modifications—for instance, competitively inhibiting methyltransferases, which significantly reduces viral replication efficiency; (3) Depleting nucleotide pools—by affecting host cell purine nucleotide synthesis pathways, thereby indirectly inhibiting viral replication; and (4) Immunomodulatory functions—including activation of the STING pathway to promote interferon production. Furthermore, this review systematically discusses the breakthrough progress in prodrug technologies for addressing key clinical challenges such as drug resistance and off-target toxicity of NAs. These advances provide crucial technical support for the clinical translation of NAs. These advances provide key technical support for the clinical translation of NAs. This review clarifies the multi-target action rules of NAs and provides a theoretical framework for the design of next-generation broad-spectrum antiviral agents.

Objective:To investigate a novel coating technology for artificial blood vessel pipelines, conducting preliminary tests on the mechanical stability, hemocompatibility, and biocompatibility of the coating.Methods:The polyester braided artificial blood vessels produced by Terumo Corporation were subjected to three different experimental treatments and divided into three groups. Model group: The uncoated artificial blood vessels were thoroughly cleaned and freeze-dried. Experimental group: The artificial blood vessels were first immersed in a dopamine solution to form a polydopamine(PDA) coating on their surface, and then further immersed in an earthworm active protein/gelatin(EWAP/GT) solution to create PDA/GT/EWAP-modified artificial blood vessels. Collagen group: The untreated polyester woven artificial blood vessels served as the control. The study detailed the characterization, porosity, water permeability, degradation rate, blood compatibility, and cytotoxicity of the PDA/GT/EWAP-coated artificial blood vessels. Additionally, a 2-week in vivo study was conducted to evaluate the biocompatibility of the PDA/GT/EWAP-coated artificial blood vessels implanted subcutaneously in SD rats.Results:The PDA/GT/EWAP-coated artificial vascular grafts were successfully fabricated. The artificial blood vessels in the PDA/GT/EWAP group exhibited a porosityof(50.53±1.10)%, with water permeability showing a gradual decreasing trend over time. The overall in vitro degradation rate at 4 weeks was(1.83±0.08)%, and the PDA/GT/EWAP group demonstrated favorable mechanical stability. The activated partial thromboplastin time(APTT) of the PDA/GT/EWAP group was(26.30±0.46)s, the thrombin time(TT) was(18.83±0.49)s, the hemolysis rate was(2.15±0.09)%, and the plasma recalcification time(PRT) was(191.00±10.54)s, indicating excellent blood compatibility and anticoagulant properties. MTT assay evaluation of the PDA/GT/EWAP group revealed no significant cytotoxicity. After subcutaneous implantation of vascular samples in rats for 2 weeks, analysis of blood immune parameters and hematoxylin-eosin(HE) staining of the artificial vascular samples showed that the immune response in the PDA/GT/EWAP group exhibited no significant difference compared to the collagen group and was superior to the model group. Conclusion.Conclusion:The PDA/GT/EWAP composite-coated artificial blood vessel demonstrates excellent mechanical properties, good hemocompatibility, biocompatibility, and low cytotoxicity. It also shows remarkable stability. This research offers a new approach for domestic technological breakthroughs in related fields.

Objective:To analyze the clinical characteristics and prognosis of primary autoimmune cerebellar ataxia (PACA) patients with autoantibodies.Methods:Patients from the Department of Neurology, Peking Union Medical College Hospital (from March 2013 to December 2023) who met the modified diagnostic criteria of PACA were collected. Cell based assay and tissue based assay were used to detect anti-cerebellar antibodies. The clinical features, results of neuroimaging, cerebrospinal fluid examinations and the prognosis of the patients were analyzed. Modified Rankin Scale (mRS) score≤2 at the last follow-up was defined as a favorable prognosis. Exacerbation of cerebellar ataxia after clinical improvement or stabilization for at least 2 months was defined as relapse.Results:A total of 20 patients were included, including 7 males. The onset age was 48.4 (22.8, 59.3) years. Gait ataxia was the most common cerebellar symptom. Extracerebellar neurological abnormalities included pyramidal sign, peripheral neuropathy/radiculopathy and diplopia. Elevated cerebrospinal fluid white blood cells and positive specific oligoclonal bands were observed in 4/16 and 7/15 of patients, respectively. The brain magnetic resonance imaging examination of the patients showed that 8 patients had no obvious abnormalities, 9 patients showed cerebellar atrophy, and 3 patients showed abnormal signals in the brain or cerebellum. A total of 9 different anti-cerebellar antibodies were detected in the patient′s serum and (or) cerebrospinal fluid, with the most common being anti-Homer-3 antibodies ( n=7). After immunotherapy, 13/17 of patients improved. After 37.5 (21.0, 93.0) months of follow-up, the median mRS score of the patients was 3, and 8 patients (8/20) achieved good prognosis and 6 patients experienced disease recurrence. Conclusions:The clinical manifestations of PACA patients have certain heterogeneity, and positive anti-neuroantibodies and meeting PACA diagnostic criteria are the main basis for diagnosing the disease. Immunotherapy is effective for most patients, but there is still a considerable proportion of patients who have not achieved a good long-term functional prognosis.

Objective:To document the effectiveness of ultrasound-guided genicular nerve block (GNB) in treating knee osteoarthritis (KOA).Methods:A total of 92 KOA patients were randomly divided into an observation group and a control group with 46 in each. Those in both groups were treated conventionally, including with non-steroidal anti-inflammatory drugs, acupuncture, ultrasound, laser irradiation and manipulation therapy. The observation group additionally underwent ultrasound-guided genicular nerve block treatment, once a week for 2 weeks. Pain scoring on a visual analog scale (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and a 6-minute walk test (6MWT) were used to evaluate everyone before and after the treatment, and then 8 weeks later.Results:In the observation group the average VAS rating [(3.54±2.00) at week 2 and (4.13±2.04) at week 8] and the average WOMAC subscale and total scores [(36.91±16.91) at week 8] had improved significantly right after the experiment and 8 weeks later. But in the control group this was true only right after the treatment. The observation group also demonstrated superior improvements in 6MWT distance at week 2 [(434.22±125.19)m] and week 8 [(446.35±126.45)m] compared to both its own baseline and the control group.Conclusions:Ultrasound-guided genicular nerve block is a rapid, precise, effective, and long-lasting intervention for alleviating pain, improving knee function and enhancing walking endurance in KOA patients.

Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

Objective To develop a Self-Report Scale of Symptoms for Post Intensive Care Syndrome-Family(PICS-F)and validate its reliability and validity,providing a scientific tool for healthcare professionals to comprehensively assess post intensive care syndrome-family.Methods Based on the symptom experience dimension of Symptom Management Theory,a preliminary version of the scale was developed through literature analysis,semi-structured interviews,expert consultations,and a pilot survey.A convenience sampling method was used to conduct the pre-trial version of the scale questionnaire survey on 442 family members of ICU patients at a tertiary A comprehensive hospital in Wuhan from June to September 2024.The test of the validity and reliability was conducted.Results The developed scale consists of 4 dimensions and 20 items.Exploratory factor analysis identified 4 factors,with a cumulative variance contribution rate of 70.921％.The content validity index at the scale level was 0.941,and the content validity indices for individual items ranged from 0.809 to 1.000.Confirmatory factor analysis indicated that the model fit indices were within acceptable ranges.The overall Cronbach's αcoefficient for the scale was 0.941,and the split-half reliability was 0.832.Conclusion The Self-Report Scale of Symptoms for PICS-F demonstrates good reliability and validity.It can comprehensively reflect the primary symptoms of PICS-F,and can serve as an effective measurement tool for clinicians to assess PICS-F in family members of ICU patients.