BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective To discuss the clinical safety,feasibility and efficacy of transcatheter arterial infusion chemotherapy(TAI)combined with lipiodol chemoembolization in the treatment of advanced colorectal cancer(CRC).Methods The clinical data of 37 patients with advanced CRC,who received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University of China between June 2016 and December 2022,were retrospectively analyzed.The clinical efficacy was evaluated,the progression-free survival(PFS)and the serious complications were recorded.Results A total of 55 times of TAI combined with lipiodol chemoembolization procedures were successfully accomplished in the 37 patients.The mean used amount of lipiodol emulsion was 2.9 mL(0.8-10 mL).No serious complications such as bleeding and intestinal perforation occurred.The median follow-up time was 24 months(range of 3-48 months).The postoperative one-month,3-month,6-month and 12-month objective remission rates(ORR)were 67.6%(25/37),67.6%(25/37),64.9%(24/37)and 56.8%(21/37)respectively,and the postoperative one-month,3-month,6-month and 12-month disease control rates(DCR)were 91.9%(34/37),91.9%(34/37),89.2%(33/37)and 81.1%(30/37)respectively.The median PFS was 16 months(range of 2-47 months).As of the last follow-up,22 patients survived and 15 patients died of terminal stage of tumor.Conclusion Preliminary results of this study indicate that TAI combined with lipiodol chemoembolization is clinically safe and effective for advanced CRC,and it provide a new therapeutic method for patients with advanced CRC.

Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

Objectives:Distolingual root of the permanent mandibular first molar(PMFM-DLR)has been frequently reported,which may complicate the treatment of periodontitis.This study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic background.Materials and methods:A total of 836 cone beam computed tomography(CBCT)images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern China.Among them,complete periodontal charts were available for 69 Chinese patients with 103 teeth.Correlation and regression analyses were used to evaluate the correlation between the morphological features of DLR,bone loss,and periodontal clinical parameters,including clinical attachment loss(CAL),probing pocket depth(PPD),gingival recession(GR),and furcation involvement(FI).Results:The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4%and 26.3%,respectively.Multiple linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section,while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal section.Conclusions:The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort.The morphological features of DLR were correlated with the periodontal status of mandibular first molars.This study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

MHNTs@PDA@ZIF-8 with rod-shaped core-shell structures was synthesized and used as sorbent in magnetic solid phase extraction(MSPE).MHNTs@PDA@ZIF-8-MSPE method coupled with gas chromatography-mass spectrometry(GC-MS)was employed to analyze sixteen kinds of polycyclic aromatic hydrocarbons(PAHs)in tea beverages.Vibrating sample magnetometer(VSM),Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD),scanning electron microscopy(SEM)and nitrogen adsorption-desorption techniques were used to characterize the MHNTs@PDA@ZIF-8.The results demonstrated that the MHNTs@PDA@ZIF-8 exhibited significant magnetic properties and a large specific surface area.The experimental conditions that could affect MSPE were investigated,including adsorbent dosage,extraction time,desorption time,ionic strength,desorption solvent type,and desorption solvent volume.The optimal conditions were 10 mg of MHNTs@PDA@ZIF-8 as adsorbent,90 s under vortex extraction,and ultrasonic desorption for 60 s with 1 mL ofn-hexane.The sixteen kinds of PAHs showed good linearity in the concentration range of 5-500 μg/L(r2≥0.995).The limits of detection(S/N=3)and quantitation(S/N=10)were in the range of 0.1-0.8 μg/L and 0.3-2.6 μg/L,respectively.The recoveries of the method ranged from 60.9%to 114.7%,with relative standard deviations(n=3)ranging from 0.2%to 9.2%when the addition levels of sixteen kinds of PAHs were 10,50,and 100 μg/L.The method was simple,fast,sensitive and environmentally friendly,and suitable for detecting sixteen kinds of PAHs in tea beverages.

Objective To investigate the effectiveness of real-time tracking and virtual reality technology(RTVI)used to assist the intraoperative alignment of the trauma orthopaedic surgery robot for the treatment of femoral neck fractures and its impact on the treatment outcome.Methods A retrospective analysis was conducted on 60 patients with femoral neck fractures treated with trauma orthopedic robotic surgery from September 2020 to September 2022.Patients were divided into two groups according to whether RTVI technology was used during surgery to assist robotic surgery.There were 28 patients in the RTVI group(12 males and 16 females),with an average age of(46.2±9.3)years old ranging from 28 to 60 years old.There were 32 patients in the simple Tianji surgical robot group,including 15 males and 17 females,aged(48.2±7.8)years old ranging from 32 to 58.The number of registered fluoroscopy,operation time,total number of intraoperative fluoroscopy,intraoperative blood loss,and hospitalization time of the two groups of patients were observed and recorded.All patients received regular follow-up after surgery,and hip X-rays were routinely reviewed to record Garden alignment index,fracture healing time,postoperative complications,and Harris score.Results All 60 patients were followed up.The RTVI group was followed up for 9 to 16 months with an average of(13.0±l.2)months,and the Tianji surgical robot group alone was followed up for 10 to 14 months with an average of(12.0±1.3)months.During the follow-up period,the femoral neck fractures of both groups of patients healed well,and no complications such as internal fixation loosening and incision infection occurred.The number of registered fluoroscopy,operation time,and number of intraoperative fluoroscopy of patients in the RTVI group were significantly better than those in the simple Tianji surgical robot group(P＜0.01).There was no statistically significant difference in intraoperative blood loss,hospital stay,Garden alignment index,fracture healing time,and hip Harris score between two groups(P＞0.05).Conclusion Although RTVI technology assisted by the surgical robot for femoral neck fracture surgery has little impact on its postoperative outcome,it can effectively reduce the operating time,the number of intraoperative X-ray projections,and the risk of intraopera-tive radiation exposure to patients.It also shortened the learning curve of the operator and better reflected the precision and ef-ficiency of the trauma orthopaedic surgery robot.

Objective Explore a non-contact physiological and psychological detection model based on facial video in simulations of weightlessness effects,research new methods for non-contact heart rate and negative mood state detection in long-term simulations of weightlessness effect analysis.Methods Construct a non-contact physiological and psychological data collection system for fusion analysis of visible light and thermal infrared videos.Collect physiological and psychological data of volunteers in the"Earth Star-Ⅱ"90-day head-down bed rest experiment.A non-contact heart rate detection model based on GCN facial multi-region feature fusion and a non-contact negative mood state detection model considering data reliability were constructed,and the effectiveness of the models were validated with finger clip heart rate and POMS-SF scale as labels.Results The experimental results show that the average difference in the Bland-Altman plot of the non-contact heart rate detection model is-1.26 bpm,and 96.3%of value error detection data falls within the 95%confidence interval,indicating a high consistency between the model detected heart rate and the finger clip heart rate.The non-contact negative mood state detection model achieves an accuracy of>0.85 for detecting tension,depression,anger,and fatigue.Features such as heart rate,AU06,eye gaze,and head pose were observed to be important to mood state detection.Conclusion Non-contact physiological and psychological detection methods not only can be utilized for long-term physiological analysis in simulations of weightlessness effects,but also provide a novel technical approach for on-orbit astronauts health assurance during long-term space flight in the future.

Objective Explore the comprehensive emotion adjustment pattern that combines non-contact physiological and psychological detection methods in fasting and low metabolism scenarios.This study aims to verify the accuracy of non-contact physiological and psychological detection algorithms and evaluate the effectiveness of multimodal emotion adjustment schemes for addressing negative emotional states such as depression and anxiety.Methods Deploy non-contact physiological and psychological detection algorithms and emotion adjustment plans to build a multimodal emotion adjustment system.Collect physiological and psychological data from volunteers participating in the 15-days complete fasting human low metabolism experiment of"Green Star Travel Ⅷ".Utilize finger clip oximeters and scales to verify the accuracy of existing non-contact physiological and psychological methods within the system.Design an emotion adjustment experiment featuring four groups:sound adjustment,acupoints adjustment,magnetism adjustment,and combination adjustment.Compare the volunteers'scale scores before and after the adjustments to verify the effectiveness of the system's emotion adjustment capabilities.Results The experimental results demonstrate that the average difference in the Bland-Altman plot for the non-contact heart rate detection model is ﹣0.497 bpm,with 95.3%of the error values falling within the 95%consistency interval.The non-contact psychological detection model achieved an accuracy rate of over 80%in identifying stress,anxiety,and depression,and an accuracy rate of over 70%in identifying fatigue and anger.Following emotion adjustment,the stress levels of the subjects significantly improved(P?