BACKGROUND:Polylactic acid(PLA)has good biocompatibility and a controllable degradation rate and is currently widely used in biomedical engineering.However,PLA has shortcomings such as low mechanical strength and insufficient biological activity,which limits its further application in bone tissue engineering. OBJECTIVE:To construct polylactic acid/polydopamine/tantalum(PLA/PDA/Ta)bone tissue engineering scaffolds,and explore their biosafety and in vitro osteogenesis. METHODS:A PLA scaffold with a porous structure was prepared through liquid crystal display light-curing technology.PLA/PDA scaffolds and PLA/PDA/Ta scaffolds were prepared by soaking PLA scaffolds in dopamine solution and dopamine-tantalum nanoparticle solution,respectively.The microstructure and water contact angle of scaffolds were characterized.MC3T3-E1 cells were co-cultured with PLA,PLA/PDA,and PLA/PDA/Ta scaffolds,respectively,and CCK-8 assay and live/dead cell staining were performed.After osteogenic differentiation,alkaline phosphatase,alizarin red staining,and osteogenic gene detection were performed. RESULTS AND CONCLUSION:(1)The scanning electron microscope results exhibited that the three kinds of prepared scaffolds had an interconnected porous three-dimensional structure,and the average pore diameter was 200 μm.The water contact angle of PLA/PDA/Ta scaffolds was lower than that of PLA and PLA/PDA scaffolds(P<0.05).(2)CCK-8 assay showed that compared with PLA and PLA/PDA scaffolds,PLA/PDA/Ta scaffolds could promote cell proliferation(P<0.05).Live/dead cell staining showed good cell proliferation in the three groups.(3)Alkaline phosphatase and alizarin red staining showed that compared with PLA and PLA/PDA scaffolds,PLA/PDA/Ta scaffolds could promote the expression of alkaline phosphatase and the formation of mineralized nodules.RT-qPCR showed that compared with PLA and PLA/PDA scaffolds,PLA/PDA/Ta scaffolds could enhance the mRNA expression of cell bone morphogenetic protein,Runx-2,and type I collagen(P<0.05,P<0.01).(4)The results showed that the PLA/PDA/Ta scaffold had excellent osteogenic activity and the ability to promote cell proliferation.

ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

It has become an industry consensus that self-assembled nanoparticles (SAN) are formed by molecular recognition of chemical components in traditional Chinese medicine during the decoction process. The insoluble components in the decoction are mostly in the form of nanoparticles, which can improve the problem of poor water solubility. However, the transfer rate of these insoluble components in the decoction is still very low, which limits the efficacy of the drug. This study aimed to refine the traditional decoction self-assembly phenomenon. The self-assembled nanoparticles were constructed by micro-precipitation method (MP-SAN), and characterized by particle size, zeta potential, stability index and morphology. The formation of MP-SAN and alterations in related physicochemical properties were evaluated using modern spectroscopic and thermal analysis techniques. The quality value transmitting pattern of lignan components within the MP-SAN was assessed via high performance liquid chromatography (HPLC). The MP-SAN showed sphere-like structure with uniform morphology, particle size of (245.3 ± 3.2) nm, polydispersity index (PDI) of (0.13 ± 0.03), zeta potential of (-48.9 ± 5.9) mV and stability index (SI) of (86.05% ± 2.27%). Comprehensive analyses using ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and other techniques confirmed molecular recognition between the decoction and ethanol extraction, leading to electron rearrangement under the influence of non-covalent bonding. This resulted in the formation of nanoparticles possessing superior thermal stability. As determined by HPLC, the encapsulation rates of the index components in the MP-SAN were all greater than 75% (dehydrodiconiferyl alcohol: 77.00%; herpetolide A: 78.57%; herpetrione: 94.53%), and the transfer rates were all higher than 65% (dehydrodiconiferyl alcohol: 96.01%; herpetolide A: 67.86%; herpetrione: 65.55%), which were 1.34, 1.38 and 4.81 times compared with those of the traditional decoction. In summary, this study successfully constructed the MP-SAN based on micro-precipitation method to achieve high transfer rate and high encapsulation rate of insoluble components in docoction, which provides a pharmaceutics idea for the efficient utilization of pharmacodynamic substance basis of traditional Chinese medicine.

BACKGROUND:Pauwels Ⅲ femoral neck fracture is a typical unstable fracture characterized by high vertical shear force and high incidence of postoperative complications.At present,there are many fixation methods for Pauwels Ⅲ fracture,and there is no clear conclusion as to which internal fixation is the best fixation method for Pauwels Ⅲ femoral neck fracture in young adults. OBJECTIVE:To compare the clinical effect of three inverted triangle cannulated screws assisted transverse lag screws and femoral neck system in fixing Pauwels Ⅲ femoral neck fractures of young adults. METHODS:From May 2021 to December 2022,21 young and middle-aged patients with Pauwels Ⅲ femoral neck fracture were treated with three inverted triangle cannulated screws assisted by transverse lag screws and femoral neck system in Affiliated Hospital of Southwest Medical University.Of them,9 patients were treated with three inverted triangle cannulated screws and one transverse lag screws perpendicular to the fracture line as the 3+1 cannulated screw group and 12 patients were treated with femoral neck system as the femoral neck system group.The two fixation methods were compared in terms of operation time,intraoperative blood loss,total incision length,intraoperative fluoroscopy times,fracture healing time,and limb function. RESULTS AND CONCLUSION:(1)All patients were followed up.Patients in the 3+1 cannulated screw group were followed up for 10-25 months,with a mean of(17.44±4.30)months.The patients in the femoral neck system group were followed up for 8-24 months,with a mean of(15.58±4.68)months.(2)The intraoperative fluoroscopy times and Harris score at 3 months postoperatively in the femoral neck system group were better than those in the 3+1 cannulated screw group,and the difference was statistically significant(P<0.05).The intraoperative blood loss,total incision length,and femoral neck shortening distance in the 3+1 cannulated screw group were better than those in the femoral neck system group,and the differences were statistically significant(P<0.05).There was no significant difference in operation time,fracture healing time,and Harris score at the last follow-up between the two groups(P>0.05).(3)It is indicated that three inverted triangle cannulated screws assisted transverse lag screw and femoral neck system can achieve good clinical effects in the treatment of young and middle-aged Pauwels Ⅲ femoral neck fracture.The femoral neck system has fewer intraoperative fluoroscopy times and better early overall stability,while the 3+1 cannulated screw is more minimally invasive,easier to operate.Both fixation methods are worthy of clinical application and promotion,and can be selected according to the actual clinical situation.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To explore the application efficacy and safety of oblique ultrasound-guided techniques in PICC puncture,in order to provide guidance and references for clinical application.Methods Through convenient sampling,654 patients from a tertiary A hospital in Zhejiang Province from March to December 2022 were selected as the study subjects.The random numbers were generated through Excel table functions and they were randomly grouped into 3 groups:A,B,and C.The ultrasound short axis method,long axis method,and oblique axis method were employed to guide PICC puncture catheterization,respectively.The success rate of PICC puncture,the number of subcutaneous adjustments of the puncture needle,puncture time,and the occurrence of puncture complications(such as hematoma,puncture of the posterior wall of blood vessels,accidental injury to arteries,and accidental injury to nerves)were recorded during the catheterization process in 3 groups.Results A total of 654 patients completed the study,including 215 in group A,219 in group B,and 220 in group C.The success rate of first-time puncture in the group C(86.36％)was higher than that in group A(73.95％)and group B(63.93％),and there was a statistically significant difference among 3 groups(P＜0.001).The subcutaneous adjustment frequency of the puncture needle was 1(1,1)in group C,1(1,2)in group A,and 1(1,2)in group B.The difference between 3 groups was statistically significant(P＜0.001);the puncture time of group C was shorter than that of group A and group B,and the difference was statistically significant(P＜0.001).There was a statistically significant difference in the puncture time between 3 groups(P＜0.017);the pairwise comparison of the number of subcutaneous needle adjustments and the success rate of a puncture between 3 groups showed that there was a statistical difference between group C and group A,and between group C and group B(P＜0.017),while there was no statistical difference between group A and group B(P＞0.017).There was statistical significance(P＜0.05)among 3 groups in terms of complications such as accidental nerve injury and puncture of the contralateral vascular wall by puncture needle,but there was no statistical significance in terms of accidental arterial injury and hematoma occurrence among 3 groups.Conclusion Compared with the short axis approach and the long axis approach,the ultrasound oblique axis approach guided PICC puncture has statistical differences in the success rate of a puncture and the incidence of puncture complications,etc.It is recommended to use the ultrasound oblique axis approach during PICC puncture.

Extracellular vesicles (EVs) are a kind of exsomes secreted by cells, which all cells release them as part of their normal physiology and during acquired abnormalities. EVs can be broadly divided into two categories by their sizes, small EVs (sEVs) and medium/large EVs (m/l EVs). As a kind of extracellular vesicle, sEVs are mostly discoid vesicles with diameters ranging from 40 nm to 200 nm. The medium/large EVs are elliptical with a diameter more than 200 nm. sEVs play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of liver diseases. In this review, we discussed the current understanding of the role of sEVs, particularly sEV derived non-coding RNA in non-alcoholic fatty liver disease (NAFLD) and their potential as diagnostic and therapeutic targets. sEVs are small membrane-bound particles secreted by cells, which fuse with plasma membrane and release to extracellular matrix. Depending on the cell of origin, sEVs could contain many cell constituents, including various DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins, biomolecules. In addition, many RNA and DNA molecules contained by sEVs, such as mRNA, microRNA (miRNA), long noncoding RNA (lncRNA) and mitochondrial DNA (mtDNA), can be transferred to recipient cells to effectively promote their biological response, physiological and pathological functions. Such sEVs-mediated responses can be disease promoting or restraining. The intrinsic properties of sEVs in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases. Recent studies reviewed here also indicate a functional, targeted, mechanism-driven accumulation of specific cellular components in sEVs, suggesting that they have a role in regulating intercellular communication. Many studies have also shown the involvement of sEVs’ noncoding RNAs (ncRNAs) in controlling cell activities and their crucial functions in regulating lipid metabolism. sEVs ncRNAs, including miRNAs, lncRNAs, and circular RNAs (circRNAs) regulate physiological functions and maintain lipid metabolism homeostasis. miRNA are small non-coding RNA molecules that regulate posttranscriptional gene expression by repressing messenger RNA-targets. These circulating miRNAs are easily accessible, disease-specific and sensitive to small changes, which makes them ideal biomarkers for diagnostic, prognostic, predictive or monitoring purposes. Specific miRNA signatures can be reflective of disease status and development or indicators of poor treatment response in liver diseases. And lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. Then circRNAs contributed to NAFLD progression by acting as miRNA sponges, functional protein sponges, or novel templates for protein translation. Finally, sEVs could be engineered to deliver diverse therapeutic payloads, including short interfering RNAs, antisense oligonucleotides and so on, with an ability to direct their delivery to a desired target. The potential of targeting sEVs with lncRNAs and miRNAs not only could be potential diagnostic biomarkers for NAFLD, but also have potential therapeutic effects on NAFLD, which might provide new ideas for the NAFLD treatment. In conclusion, this review provides an overview of the current understanding of the roles of sEVs ncRNAs in NAFLD, so we suggest that further research into sEVs could lead to new diagnostic tools and therapeutic strategies for NAFLD.

【Objective】 To comprehensively explore the serological characteristics of anti-PP1P^k and potential therapeutic strategies for recurrent miscarriage in p-blood type pregnant women. 【Methods】 Neutralization with pigeon egg white and human plasma, disruption of IgM antibodies by 2-mercaptoethanol reagent, and complement adding were conducted. Anti-PP1P^k titers under different processing conditions, media and temperatures were determined, and neutralizing effect of human plasma on anti-PP1P^k and its sensitization complement ability were analyzed. 【Results】 The titers of anti-PP1P^k in saline and column agglutination were 4 and 8, respectively. Low temperature increased titers, while β-mercaptoethanol treatment significantly reduced them. Pigeon egg white partially neutralized anti-PP1P^k antibodies. Human plasma was also capable of reducing anti-PP1P^k titers with neutralization capability surpassing that of pigeon egg white, and there were individual differences in neutralization capability. 【Conclusion】 The anti-PP1P^k was a blend of antibodies encompassing both IgM and IgG types, exhibiting cold reactivity, and having the potential for complement activation. Human plasma emerges as an effective modulator for diminishing the efficacy of anti-PP1P^k. Plasma transfusion holds promise as a therapeutic avenue for addressing recurrent miscarriages in pregnant individuals with the p phenotype.

ObjectiveTo explore the research status and hot spots of virtual reality in the field of stroke rehabilitation. MethodsThe literature related to the application of virtual reality technology in stroke rehabilitation was retrieved in CNKI and Web of Science core collection from establishiment to August, 2024. The knowledge map of authors, institutions and keywords was drawn by Citespace 6.2.R7. ResultsA total of 485 papers were retreived, including 201 in Chinese and 284 in English. The number of articles published in both Chinese and English was on the rise. Qu Yun was the Chinese author with the most articles, and Rocco Salvatore Calabro was the English author. The Third Affiliated Hospital of Sun Yat-Sen University and IRCCS Bonino Pulejo published the most papers respectively. The results of keyword co-occurrence and clustering were consistent in the Chinese and English keywords, mainly included hemiplegia, balance function, upper limb function and cognitive function. The keywords with high bursting intensity in Chinese included motor function, cognitive function and upper limb function, while those with high bursting intensity in English included upper limb, cognitive impairment and environment. The hot spots in this field focused on the virtual reality technology for stroke patients' motor function rehabilitation, cognitive function rehabilitation, limb function rehabilitation and virtual reality technology combined with conventional treatment. ConclusionVirtual reality technology, as a simulation information technology, has been widely applied in the fields of motor function rehabilitation, cognitive function rehabilitation and limb function rehabilitation for stroke patients. The combination of virtual reality technology with conventional rehabilitation therapy could enhance the functional level and activities of daily living. More researches may focus on conjunctions of virtual reality technology with new technologies such as digital therapeutics and brain-computer interfaces, to improve the gait and upper limb functions of stroke patients.

Objective To explore the therapeutic value of metoprolol combined with Wenxin Keli(a Chinese patent drug)on atrial tachycardia(AT)after catheter ablation in patients with atrial fibrillation(AF).Methods A total of 290 patients who were diagnosed with AF and underwent catheter ablation successfully in the Department of Cardiovascular Medicine of Northern Jiangsu People's Hospital from May 2018 to January 2022 were enrolled,and were randomly divided into Wenxin Granule group(Group W),metoprolol group(Group M),combined group(Group MW)and blank control group(Group C).The times of AT,heart beats during the longest AT episode,average heart rate and adverse reactions were compared among the 4 groups.Results The mean heart rate,episodes of AT,heart beats during the longest AT episode,and numbers of premature atrial contractions(PAC)of class Ⅰ,Ⅱ and Ⅲ in Group C in 1 year after operation were all sig-nificantly higher than the baseline levels(P＜0.01),so were in the Group W,Group M and Group MW(P＜0.01).Group MW had obviously lower mean heart rate,episodes of AT,heart beats dur-ing the longest AT episode,and numbers of PAC of class Ⅰ,Ⅱ and Ⅲ when compared with Group W and Group M(P＜0.05).There was no significant difference in the total incidence of ad-verse reactions in Group W,Group M and Group MW(7.1％vs 13.9％vs 8.9％,P=0.301).Con-clusion Metoprolol combined with Wenxin Keli can be used to treat AT after AF catheter abla-tion.The combination can effectively reduce the average heart rate,episodes of AT,numbers of PAC and heart beats during the longest AT episode,and thus decrease the recurrence of postopera-tive AF with high safety.