Enhanced uptake and anti-maturation effect of celastrol-loaded mannosylated liposomes on dendritic cells for psoriasis treatment

Psoriasis is an autoimmune skin disease in which dendritic cells (DCs) trigger the progression of psoriasis by complex interactions with keratinocytes and other immune cells. In the present study, we aimed to load celastrol, an anti-inflammatory ingredient isolated from Chinese herbs, on mannosylated liposomes to enhance DC uptake as well as to induce DC tolerance in an imiquimod-induced psoriasis-like mouse model. Mannose was grafted onto liposomes to target mannose receptors on DCs. The results demonstrated that compared with unmodified liposomes, DCs preferred to take up more fluorescence-labeled mannosylated liposomes. After loading celastrol into mannose-modified liposomes, they effectively inhibited the expression of maturation markers, including CD80, CD86 and MHC-II, on DCs both in vitro and in vivo. Additionally, after intradermal injection with a microneedle, celastrol-loaded mannose-modified liposomes (CEL-MAN-LPs) achieved a superior therapeutic effect compared with free drug and celastrol-loaded unmodified liposomes in the psoriasis mouse model in terms of the psoriasis area and severity index, histology evaluation, spleen weight, and expression of inflammatory cytokines. In conclusion, our results clearly revealed that CEL-MAN-LPs was an effective formulation for psoriasis treatment and suggested that this treatment has the potential to be applied to other inflammatory diseases triggered by activated DCs.

Network pharmacology and molecular docking analysis on molecular targets and mechanism prediction of Huanglian Jiedu Decoction in the treatment of COVID-19 / 数字中医药（英文）

@#Objective To investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction (黄连解毒汤, HLJDD) in the treatment of Corona Virus Disease 2019 (COVID-19) through network pharmacology and molecular docking analysis. Methods The chemical constituents and action targets of HLJDD were retrieved on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SymMap v2, Encyclopedia of Traditional Chinese Medicine (ETCM), a High-throughput Experiment- and Reference-guided Database of Traditional Chinese Medicine (HERB), and Traditional Chinese Medicine Integrated Database (TCMID). UniProt and GeneCards were used to query the target genes that corresponding to the active compounds, and then a compound-target network was constructed using Cytoscape 3.7.2. Gene Ontology (GO) database was used to annotate GO functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to predict the possible mechanisms of active compounds. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to analysis the tissue enrichment. The main active compounds in HLJDD are molecularly docked with their corresponding related targets. Results Seventy-six compounds were screened and 458 corresponding targets in the network were obtained. Gene annotation showed that the targets were involved mainly in 1 953 biological processes. 884 signaling pathways was enriched, involving signaling by interleukins, cytokine signaling in immune system, generic transcription pathway, and RNA polymerase II transcription. The targets mainly distributed in the lung, liver, and placenta, involving a variety of immune cells, such as T cells and B cells. The molecular docking results showed that core compounds such as wogonin, berberine, and baicalein had high affinity with tumor necrosis factor (TNF), insulin (INS), and tumor protein 53 (TP53). Conclusion The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as vascular endothelial growth factor A (VEGFA), INS, interleukin-6 (IL-6), TNF, caspase-3 , TP53, and mitogen-activated protein kinase 3 (MAPK3).

Uptake and trafficking of different sized PLGA nanoparticles by dendritic cells in imiquimod-induced psoriasis-like mice model

Psoriasis is an autoimmune inflammatory disease, where dendritic cells (DCs) play an important role in its pathogenesis. In our previous work, we have demonstrated that topical delivery of curcumin-loaded poly (lactic-

Application of 3D Printing Combined with S-ROM Total Hip Arthroplasty in the Treatment of Adult Crowe Ⅳ DDH / 昆明医科大学学报

Objective To investigate the application of 3D printing combined with S-ROM total hip arthroplasty in the treatment of adult Crowe IV DDH. Methods Between September 2014 and June 2017, 10 patients of adult Crowe IV DDH were selected and divided into 3D group (5 cases) and non-3D group (5 cases) . There were 4 males and 6 females with an average age of 43.6 years (range,27-63years) . Harris scores were recorded in both groups before the operation, and in the group 3D, patients underwent spiral CT scanning to make the hip 3D models. According to the hip 3D models, the sizes of prosthesis and operation schemeswere estimated before the operation ,and the surgery simulation was performed. Then the S-ROM prosthesis was used for total hip arthroplasty. The actual situation of hip joint, the size of prosthesis,time of operation and blood loss were recorded.Harris Score at 1 week post-operationwere recorded again. All patients were followed up related postoperative complications for at least 2 weeks.Results The 3D printing models coordinated with the actual sizes of the hips in the3D group.The time of operation and blood loss were less than the non-3D group. Higher Harris score was observed at 1 week post-operation in the 3D group,compared to non-3D printing group.The follow-up showed that the motion of the hips was improved obviously. Conclusion The Application of 3D Printing combined with S-ROM total hip arthroplasty in the treatment of adult crowe IV DDH can improve efficiency and accuracy of the operation, shorten time of operation , reduce operative blood loss and rate of complications.

Microbiological and parasitological investigation of experimental minipigs in Guangdong province / 中国比较医学杂志

Objective To conduct a microbiological and parasitological investigation of experimental minipigs in Guangdong province. Methods Four major experimental minipig production units in Guangdong province were included in this investigation. Samples were taken from a total of 154 pigs of 4 brreds, i. e. , Bama minipigs, Juema minipigs, Tibet minipigs and Wuzhishan minipigs. Pig fur, scales, serum, rectal swabs and feces samples were collected for detection of 20 pathogens. The data were analyzed and compared among the production units and breeds. Results Mixed infections were detected in all the four institutions. The infection rates of 7 pathogens were rather high: Streptococcus suis type 2 (50. 7%), Actinobacillus pleuropneumoniae (40. 3%), Mycoplasma hyopneumoniae (100%), Japanese encephalitis virus (41. 3%), porcine circovirus type 2 (74. 8%), porcine transmissible gastroenteritis virus (73. 8%),gastroenteritis virus (44. 7%). Porcine parvovirus (26. 0%), pseudorabies virus(15. 6%) and intestinal worms (3. 2%) were also detected in some animals. The immune qualified rates of classical swine fever virus (62. 8%) and foot-and-mouth disease virus (35. 8%) were rather low. The immune qualified rate of pseudorabies virus was as high as 98. 4%. Besides, Salmonella, Brucella, swine dysentery snake like spirochetes, dermatophytes, influenza virus. Toxoplasma gondii, ectoparasites, and coccidia were not detected. Conclusions The results of this investigation indicate that epidemiological quality control of pathogens in experimental minipigs and efforts to establish high grade minipig population in Guangdong province remain to be strengthened. Our study also provides a basis for revision of local and even national standards for experimental minipigs.

Microbiological and parasitological investigation of experimental minipigs in Guangdong province / 中国比较医学杂志

Objective To conduct a microbiological and parasitological investigation of experimental minipigs in Guangdong province. Methods Four major experimental minipig production units in Guangdong province were included in this investigation. Samples were taken from a total of 154 pigs of 4 brreds, i. e. , Bama minipigs, Juema minipigs, Tibet minipigs and Wuzhishan minipigs. Pig fur, scales, serum, rectal swabs and feces samples were collected for detection of 20 pathogens. The data were analyzed and compared among the production units and breeds. Results Mixed infections were detected in all the four institutions. The infection rates of 7 pathogens were rather high: Streptococcus suis type 2 (50. 7%), Actinobacillus pleuropneumoniae (40. 3%), Mycoplasma hyopneumoniae (100%), Japanese encephalitis virus (41. 3%), porcine circovirus type 2 (74. 8%), porcine transmissible gastroenteritis virus (73. 8%),gastroenteritis virus (44. 7%). Porcine parvovirus (26. 0%), pseudorabies virus(15. 6%) and intestinal worms (3. 2%) were also detected in some animals. The immune qualified rates of classical swine fever virus (62. 8%) and foot-and-mouth disease virus (35. 8%) were rather low. The immune qualified rate of pseudorabies virus was as high as 98. 4%. Besides, Salmonella, Brucella, swine dysentery snake like spirochetes, dermatophytes, influenza virus. Toxoplasma gondii, ectoparasites, and coccidia were not detected. Conclusions The results of this investigation indicate that epidemiological quality control of pathogens in experimental minipigs and efforts to establish high grade minipig population in Guangdong province remain to be strengthened. Our study also provides a basis for revision of local and even national standards for experimental minipigs.

Formula Optimization of Memantine Hydrochloride Sustained Release Pellets by Box-Behnken Surface Response Design / 中国药师

Objective: To optimize the formula of memantine hydrochloride sustained release pellets and investigate the drug release in vitro.Methods: Memantine hydrochloride sustained release pellets were prepared by a fluidized bed.The factors such as inlet air temperature, spray pressure and feeding rate were optimized by orthogonal tests.The Box-Behnken response surface methodology was used to screen the major influencing factors (ethyl cellulose aqueous dispersion, PEG 6000 and the coating weight) in the release of memantine hydrochloride.The coating formula and coating weight were optimized with the cumulative release rate of memantine hydrochloride in 2, 6,and 12 h as the response values.The drug release in vitro was also studied.Results: The optimum preparation parameters of the pellets were as follows: the inlet air temperature of 45℃, the spray pressure of 1.0 bar, and the feeding rate of 1.5 r·min-1.The best sustained release coating formula was as follows: the content of ethyl cellulose aqueous dispersion of 8.4%, the content of PEG 6000 of 2.3%, and the weight gain of sustained release layer of 16.7%.The memantine hydrochloride sustained release pellets had notable sustained release effect.Conclusion: Orthogonal tests and Box-Behnken response surface method can be used for the formula optimization of memantine hydrochloride sustained-release pellets.The established fitting model is simple with good predictability.

A case report of diffuse pneumocephalus induced by sneezing after brain trauma / 中华创伤杂志(英文版)

Pneumocephalus is the presence of air in the cranial vault. The common etiologies of pneumocephalus are brain trauma and cranial surgery. We report a case of a 26-year-old man with brain trauma who developed diffuse pneumocephalus after sneezing. CT scan was performed on arrival, and the image showed subarachnoid hemorrhage without pneumocephalus. On the seventh day after a big sneeze brain CT scan was re-performed, which showed pneumocephalus. After another ten days of treatment, the patient was discharged without any symptoms.

Impact of artesunate on the expression and secretion of transforming growth factor-b1 of primary rat hepatic stellate cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the impact of the Artemisia annua plant-derived drug, artesunate, on proliferation of primary rat hepatic stellate cells (HSCs), and to analyze the underlying molecular mechanisms of its anti-fibrogenic effects involving the inhibition of transforming growth factor-beta 1 (TGF-b1) expression and secretion in liver.</p><p><b>METHOD</b>Isolated, cultured, and activated primary rat HSCs were divided into sixteen groups, including one untreated control group and fifteen artesunate-treated experimental groups with 125, 150, 175, 200 or 225 mumol/L for 24, 48 or 72 hours. The rate of cellular proliferation was measured using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. TGF-b1 mRNA expression was evaluated by reverse transcription-polymerase chain reaction and protein expression was evaluated by Western blotting. Enzyme-linked immunosorbent assay was used to evaluate secreted levels of TGF-b1 protein.</p><p><b>RESULTS</b>Artesunate significantly inhibited proliferation of cultured HSCs in a dose- and time-dependent manner (all, P less than 0.01). After 24 hours of exposure, the inhibition ratios of the various artesunate concentrations were: 6.06%+/-1.44% (125 mumol/L), 21.47%+/-5.57% (150 mumol/L), 42.00%+/-7.36% (175 mumol/L), 67.12%+/-4.55% (200 mumol/L), and 79.83%+/-3.67% (225 mumol/L). Artesunate significantly inhibited the TGF-b1 mRNA expression in HSCs, and the higher the drug concentration, the higher the degree of inhibition (all, P less than 0.01). In addition, artesunate significantly inhibited the expression of intracellular and secreted TGF-b1 protein (all, P less than 0.01). In response to artesunate (mumol/L concentrations), the TGF-b1 levels were (164.24+/-6.88) pg/ml (0μmol/L), (102.68+/-4.45) pg/ml (150μmol/L), (86.54+/-5.56) pg/ml (175μmol/L), and (56.55+/-5.66) pg/ml (200μmol/L).</p><p><b>CONCLUSION</b>Artesunate exerts anti-fibrogenic effects on HSCs in vitro, possibly by reducing the expression, translation and secretion of TGF-b1.</p>

Combined procedure for the treatment of ankle and foot deformities secondary to spina bifida / 中国骨伤

<p><b>OBJECTIVE</b>To study surgical strategies for ankle and foot deformities secondary to spina bifida and treatment methods for different types of deformities.</p><p><b>METHODS</b>From January 1990 and July 2009, 107 patients with ankle and foot deformities secondary to spina bifida were retrospectively analyzed. There were 44 males and 63 females, with an average age of 17.7 years (rangd from 1.3 to 52 years). Among the patients, 58 patients had double ankle deformities, 49 patients had unilateral deformities (22 cases on the left side, 27 cases on the right). Ninety-nine patients with equinus deformities were treated by achilles tendon lengthening and tendon transfering; 25 patients with talipes were treated by release of anterior tendon of ankle and tendon transfer; 17 patients with valgus and varus deformities were treated by tendon transfer and calcaneal osteotomy; 15 patients with flail deformities were managed treated by bone fusion between calcaneus and talus and shortening of achilles tendon; 9 patients with claw toe deformities were treated by bone fusion of interphalangeal joint or Ilizarovs distraction. AOFAS (American Orthopaedic Foot & Ankle Society) comprehensive scoring system was used to evaluate subjective pain and objective functional.</p><p><b>RESULTS</b>Seventy-nine (127 feet) of 107 patients were followed up, and the duration ranged from 48 to 180 months (averaged, 64 months). According to AOFAS scoring system, the results were rated as excellent in 89 feet, good in 26 feet, moderate in 9 feet and poor in 3 feet.</p><p><b>CONCLUSION</b>Treatment strategies for ankle-foot deformities mainly included four principles, deformity correction, muscular balance, joint stability and reservation of foot elasticity. Different combined procedure was applied for different foot deformities and received good therapeutic effects.</p>

Analysis of middle-term outcome of the imaging characteristics after the percutaneous laser disc decompression / 中华外科杂志

<p><b>OBJECTIVE</b>To study the imaging findings outcome of the percutaneous laser disc decompression (PLDD) and evaluate the middle-term safety and efficacy of PLDD.</p><p><b>METHODS</b>The imaging data of 22 cases suffered cervical spondylosis or lumbar spondylosis and treated by PLDD more than 3 years were retrospectively reviewed. To observe the intervertebral space of the invasive disc and the intervertebral disc hernia before and after the operation on the lateral projection of X-ray and the axial view of the MRI. To make a statistical analysis of the data.</p><p><b>RESULTS</b>There was no obvious change of disc height involving the anterior disc height, the intermediate disc height and the posterior disc height after the PLDD at the final follow-up (P > 0.05). At last time follow-up, the Sagittal Index (SI) are 0.10 - 0.54 and 0.06 - 0.39 before and after the PLDD in the treatment of cervical vertebra. The statistical difference were significant (P < 0.05). In lumbar vertebra, the SI is 0 - 0.71 and 0 - 0.48 disc before and after the PLDD. The statistical difference were very significant (P < 0.01).</p><p><b>CONCLUSIONS</b>The PLDD will not destroy the intervertebral space of the cervical and lumbar vertebra obviously; moreover, it can effectively reduce the disk hernia. The PLDD is a safe and effective Mini-invasive surgery for cervical vertebra and lumbar vertebra diseases.</p>

The strategy of posterior decompression and re-establishing the insertion of extensor for ossification of posterior longitudinal ligament involved in C(2) / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate an approach of posterior cervical spinal canal decompression and re-establishing the insertion of extensor, aim at the ossification of the posterior longitudinal ligament (OPLL) involved in C(2).</p><p><b>METHODS</b>From 2002 to 2006, 10 patients with OPLL involved in C(2) underwent open-door laminoplasty, with the posterior cervical ligamentous complex and the insertion of extensor reconstructed on C(2), were reviewed retrospectively. The range of decompression was from C(2) to C(7). The sagittal diameter of C(2) vertebral canal, alignment of the cervical spine (C(2)-C(7) angle), and JOA score before and after operation were contrasted respectively.</p><p><b>RESULTS</b>All patients were followed up, average 14 months. Before the operation, the average sagittal diameter of C(2) vertebral canal was 5.6 mm (4 - 8.8 mm), JOA score was 9.6 scores (6 - 12 scores), C(2)-C(7) angle was 6.5 degrees (-2 degrees - 12 degrees ). After the operation, the average sagittal diameter of C(2) vertebral canal was 13.4 mm (10 - 18.2 mm, P < 0.01), JOA score was 10.9 scores (8 - 14 scores) and the C(2)-C(7) angle was 7.4 degrees (3 degrees - 14 degrees ) in earlier. Finally, the JOA score was 13.2 scores (10 - 17 scores, P < 0.05), and the C(2)-C(7) angle was 7.0 degrees (2 degrees - 15 degrees , P > 0.05) at last.</p><p><b>CONCLUSIONS</b>The open-door laminoplasty, with an approach of the posterior cervical ligamentous complex and the insertion of extensor reconstructed, is an appropriate method for treating OPLL involved in C(2). This process keeps the cervical curve in a better way, and decompresses the spinal canal effectively.</p>

Anatomical and clinical study of the supinator syndrome evoked embitterment test / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the mechanism and feasibility of the supinator syndrome evoked embitterment test from anatomy and clinic.</p><p><b>METHODS</b>25 cases of The supinator syndrome were reviewed. 18 of them were male and 7 were female. Drop finger deformation were apparent in 25 cases and The supinator syndrome evoked embitterment test was positive for All patients. Operative neurolysis was done in 8 cases, conservation treatment 17 cases; 92 cadaver upper extremities were dissected for a study the relationship between supinator tunnel and posterior interosseous nerve.</p><p><b>RESULTS</b>22 cases had been followed up for an average of 9 months. 16 cases had a full recovery and 6 cases, a partial recovery. the anatomical study shows that The posterior interosseous nerve was compressed by Forhse arcade and the distal border of the supinator muscle during passive pronation forearm.</p><p><b>CONCLUSION</b>The supinator syndrome evoked embitterment test was a new test for the diagnosis of supinator syndrome, it was found to be more sensitive and specific than the others test.</p>