To improve the targeted therapeutic effect of magnolol (Mag) on neuroblastoma, Mag-loaded mitochondria-targeting immunoliposomes modified by datuximab (aGD2) and triphenylphosphine (TPP) (Mag/aGD2-T-ILN) were prepared, and their physicochemical properties, targeting characteristics and anti-tumor activity were evaluated. Physico-chemical properties showed that the surface of Mag/aGD2-T-ILN was smooth and spherical, with good dispersibility. The particle sizes, PDI and Zeta potentials of Mag/aGD2-T-ILN were measured to be (136.5 ± 5.1) nm, 0.184 ± 0.010 and (27.5 ± 3.6) mV, respectively. Mag/aGD2-T-ILN could release the drug continuously and slowly, and maintain good stability at 4 ℃. Cytotoxicity test exhibited that the IC50 of 2-ME/aGD2-T-ILN was (4.07 ± 0.48) µmol/L, and compared with free Mag, the toxicity of Mag/aGD2-T-ILN to SH-SY5Y cells increased by 6.4 times. Cellular binding and uptake assays suggested that Rho-aGD2-T-ILN could specifically target GD2-positive tumor cells and then further reach their mitochondria. Therapeutic efficacy indicated that Mag/aGD2-T-ILN could better suppress the growth of SH-SY5Y tumor cells in the body with lower toxicity and less side-effects. The results demonstrated that the Mag/aGD2-T-ILN nanoparticles system could achieve intracellular endocytosis through specific binding of antibodies and antigens between the carrier and the surface of tumor cells and electrostatic interaction, then effectively delivered and released the drugs into mitochondria by crossing the mitochondrial phospholipid membrane through TPP, and thus achieving mitochondria-targeting therapy of Mag/aGD2-T-ILN. Through the construction of this active targeting delivery system, the clinical application value of datuximab and Mag is improved, providing a novel approach for the clinical treatment of neuroblastoma.

Objective To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. Methods All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. Results A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. Conclusions The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

Background Prolonged awkward postures during occupational activities can lead to excessive musculoskeletal load on the wrist of workers and symptoms such as wrist pain or discomfort. Objective To survey the prevalence of wrist pain among workers in 10 key industries and analyze its correlation with wrist working postures. Methods By using stratified cluster sampling method, workers from 10 key industries, such as footwear manufacturing industry, shipbuilding manufacturing industry, and automobile manufacturing industry, were selected from seven regions in North China, East China, Central China, South China, Southwest China, Northwest China, and Northeast China. The demographic information, wrist working postures, pain in wrist of the workers were collected through a cross-sectional survey. Pearson χ² test was used to compare prevalence by selected factors, trend χ² test for between group comparison, and unconditional logistic regression models for the association of wrist working postures with wrist pain. Results There were 64052 workers enrolled in this survey, and 56286 provided valid questionnaires (the effective rate was 87.8%). According to the survey, the prevalence of wrist pain was 23.3% (13112/56286), and the industries with higher prevalences were footwear manufacturing (27.1%, 1927/7106), automobile manufacturing (24.9%, 5378/21560), and shipbuilding and related equipment manufacturing (24.4%, 850/3488) industries. Finger pinching (OR=2.09, 95%CI: 1.95-2.24), frequent wrist bending (OR=2.03, 95%CI: 1.92-2.15), fixed wrist bending (OR=1.77, 95%CI: 1.69-1.85), wrist on hard edge (OR=1.34, 95%CI: 1.28-1.40), and arms over shoulders (OR=1.11, 95%CI: 1.05-1.17) increased the risk of reporting wrist pain. Conclusion Awkward postures are related to wrist pain among workers in selected 10 key industries. The related factors are wrist on hard edge, frequent wrist bending, finger pinching, fixed wrist bending, and arms over shoulders.

Objective: To analyze the current status of work-related musculoskeletal disorders (WMSDs), work fatigue and musculoskeletal pain in Chinese occupational population, and to study the relationship between work fatigue and musculoskeletal pain and WMSDs. Methods: A total of 66 961 employees from 323 enterprises in 15 key industries in China were selected as the study subjects using stratified cluster sampling method. The incidence of WMSDs in the past year was investigated using the Chinese version of the Musculoskeletal Disorders Questionnaire, and the work fatigue and musculoskeletal pain were investigated using Borg 6-20 Rating of Perceived Exertion Scale and visual analogue scale. The data were standardized using the age composition data of 18 to 60 years from the seventh national population census. Results: The standardized annual incidence of WMSDs was higher in the front-line workers than that in the administrative and other supportive staff (38.82% vs 36.30%). The detection rates of work fatigue and musculoskeletal pain in the study subjects were 44.54% and 63.08%, respectively. The result of S-curve fitting showed that the risk of WMSDs increased with the level of work fatigue (P<0.01). Among the front-line workers, the average of monthly fatigue frequency in the neck, shoulder, lower back, upper back, wrist/hand, foot and ankle, knee, leg, and elbow were higher in the group with WMSDs compared to those without WMSDs (all P<0.01). The pain degree of musculoskeletal pain was higher in all nine sites in the fatigued group than in the no-fatigue group (all P<0.01). The standardized detection rate of musculoskeletal pain was higher in the fatigued group than in the non-fatigued group (80.38% vs 25.71%). The work fatigue was moderate and positively correlated with musculoskeletal pain in all seven sites except the lower back and elbow, with Kendall Tau-b correlation coefficients ranging from 0.423 to 0.546 (all P<0.01). Conclusion: There is a good correlation between work fatigue and local musculoskeletal pain, work fatigue and WMSDs in Chinese occupational population. Implementing ergonomic interventions to control the development of work fatigue can be an effective measure for preventing WMSDs.

OBJECTIVE：To investigate the situ ation and characteristics of ADR reports in the elderly patients （≥65 years old ） of Sichuan province ，and to provide reference for guaranteeing the safety of drug use. METHODS ：ADR reporting data of elderly patients collected by spontaneous reporting system of Sichuan ADR monitoring center from 2013 to 2019 were collected ，and then analyzed in respects of report types ，reproting institution ，relationship，patienst’age，gender，nationality，drug type ，organ/system invovled. RESULTS & CONCLUSIONS ：In the past seven years ，175 431 cases spontaneous ADR were collected by Sichuan ADR monitoring center ，and the annual proportion of “general”ADR reports decreased from 78.93％ in 2013 to 60.50％ year by year ； the annual proportion of “new general ”and“serious”ADRs increased year by year ，among which that of “new general ”ADR increased more obviously. The main reporting institutions were medical institutions ，accounting for 92.79％-98.87％ of the total annual reports. The enthusiasm of enterprises and individuals to report ADR needed to be improved ；8 031 cases（4.58％）were “positive”relationship，21 283 cases（12.13％）were“likely”，146 117 cases（83.29％）were“possible”. Except that the gender of 272 cases were not reported ，there were 88 176 male cases and 86 983 female cases ；most of them were 65-74 years old （104 962 cases，59.83％）. The reports covered 19 nationalities，among which the re were 166 752 cases（98.72％）of Han nationality. The distribution of ADR related drug categories in elderly patients of Yi ， Tibetan and Qiang nationalities was significantly different from that of Han nationality （P＜0.01）. The top three drug categories in the total frequency were anti-infective drugs （31.10％），traditional Chinese medicine com （18.27％），and central nervous system drugs （9.99％）. The injection route was the most likely to cause ADR （72.12％）. ADR mainly involved s kin and its appendants （21.47％）， gastrointestinal system （19.61％）and central and peripheral nervous system （18.55％）. Aminophylline injection was the only dr ug in the top 10 drugs leading to “new general ”ADR for consecutive 7 years. Cefotaxime sodium for injection ，Ceftriaxone sodium for injection ，Cefoperazone sodium and sulbactam sodium for injection were the top 10 drugs causing “severe”ADR in consecutive 7 years，which should be paid more attention in clinic.

Objective To observe NLS-KALA-SA-PTX (NKSP) for lung adenocarcinoma cell line A549 in vitro with paclitaxel monotherapy, and the mechanism thereof. Methods MTT assay was used to detect A549 cell proliferation influ-enced by different concentrations of NKSP (20, 40, 80, 100μg/L) and paclitaxel monotherapy (20, 40, 80, 100μg/L) for 24 h, 48 h and 72 h.. Subsequent experiments were divided into four groups, namely, group A (without any drug treatment), group B (added polypeptide 80μg/L of self-assembled nanoparticles, NKS), group C (80μg/L paclitaxel monotherapy) and group D (80μg/L NKSP). Flow cytometry was used to detect the cell apoptotic rates after 48 h and 72 h treatment in four groups. Western blot assay was used to analyse the protein expressions of bax and caspase-3 after 48 h and 72 h treatment in four groups. Results Both paclitaxel monotherapy and NKSP can inhibit the proliferation of A549 cells. The inhibitory rates of paclitaxel monotherapy group at 48 h and 72 h and NKSP group at 72 h showed an increasing trend in a dose-depen-dent manner (P<0.05). After treatment for 48 hours, the apoptotic rate was significantly higher in D group than that of C group (P<0.05). But the apoptotic rate at 72 h was lower in D group than that of C group (P<0.05). The protein expressions of bax and caspase-3 at 48 h were significantl lower in D group than those of C group, which were higher at 72 h in D group than those of C group (P<0.05). Conclusion Compared to paclitaxel monotherapy group, NKS promotes slow release of pa-clitaxol, which reduces the cytotoxicity and extends the antitumor effects.

Objective To evaluate the platelet adhesion ability on pure titanium surfaces modified with different techniques.Methods Pure titanium specimens were treated with 5 different surface modification techniques,including machine polish(MP),dual acid-etch(DAE),sandblast-large grit and acidetch(SLA),micro-arc oxidation(MAO) and anodized titania nanotube(TNT).The surface topographies of specimens were observed by scanning electron microscopy(SEM).Chemical compositions,surface roughness and static water contact angle of specimens were detected by energy dispersive spectrometer(EDS),laser scanning confocal microscope(LSCM) and contact angle analyzer respectively.Platelets were cultured on specimen surfaces for 30 min.The amount and viability of adhered platelets adhered were evaluated.Platelet distribution and morphology were observed by LSCM and SEM.Results Surface topographies of the five groups of specimens differed significantly.MP,DAE,SLA and MAO surfaces showed micro-scale topographies,while TNT surfaces showed nano-scale topography with nanotubes at the diameter of (80.46± 0.35) nm.The surface roughness of MAO was the highest among the 5 groups.TNT surfaces demonstrated the lowest roughness as well as the lowest static water contact angle as 13.55°± 0.96°.The amount of platelets adhered on TNT surface was the greatest as (300 729±8 325) platelet/μl and the viability was the highest(A450 value 2.14±0.05).Platelet adhered intensively on TNT surfaces,forming pseudopodia,extending and connecting with each other.Conclusions Surface properties of pure titanium affect platelet adhesion ability.Nano-scale topography can greatly improve platelet adhesion.Increased surface roughness and hydrophilicity can improve platelet adhesion ability.

Objective To study the incorporation rate and release behavior of bovine serum albumin(BSA) incorporated into the calcium phosphate coating by biomimetic deposition,as well as the physical and chemical properties of the hybrid coating,and to provide experimental basis for the fabrication of growth factor/biomimetic calcium phosphate coating and exploration for the loading/release behavior of growth factors.Methods Pure titanium specimens were immersed into saturated calcium phosphate solutions(SCP) containing no BSA(controlled group) and 3 different concentrations of BSA(experimental groups):1,10 and 100 mg/L.Biomimetic calcium phosphate coating was formed on titanium surface and BSA was incorporated into the coating through co-deposition.The topography of the specimen was observed using scanning electron microscopy(SEM).Chemical structure and phase composition of coatings were detected by Fourier infrared spectroscopy(FTIR) analysis and X-ray diffraction(XRD) respectively.BSA incorporation rate and release profile were determined by bicinchoninic acid protein assay kit.Results The biomimetic calcium phosphate coating was mainly composed of hydroxyapatite and octacalcium phosphate.BSA was successfully incorporated into the calcium phosphate coatings in all the 3 experimental groups.With the increase of BSA concentration,plate-like units of the coatings were turned into small grid structure.BSA incorporation rates of the three experimental groups were(72.4 ± 2.4)％,(62.3 ± 0.9)％ and (42.2 ± 1.7)％ respectively.The in vitro release test showed that all three BSA release profiles could be divided into two significant different stages:early burst release stage and later sustained release stage.The amount of BSA release of the 3 experimental groups in 24 h and 30 d were (1.57±0.09),(8.82±0.93),(140.24±3.12) μg,and (2.39±0.29),(14.39±0.70),(151.06±2.00) μg respectively.Conclusions Biomimetic calcium phosphate coating can be used as an effective carrier for protein.BSA concentration has an impact on the incorporation rate and release speed of BSA from the calcium phosphate coating.Favorable BSA incorporation rate and release behavior can be obtained at BSA concentration of 10 mg/L.