BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

Objective To investigate the effectiveness of the integrated schistosomiasis control programme in Sichuan Province during the stage moving from transmission interruption to elimination (2015—2023), so as to provide insights into formulation of the schistosomiasis control measures during the post-elimination stage. Methods Schistosomiasis control data were retrospectively collected from departments of health, agriculture and rural affairs, forestry and grassland, water resources, and natural resources in Sichuan Province from 2015 to 2023, and a database was created to document examinations and treatments of human and livestock schistosomiasis, and snail survey and control, conversion of paddy fields to dry fields, ditch hardening, rivers and lakes management and building of forests for snail control and schistosomiasis prevention. The completion of schistosomiasis control measures was investigated, and the effectiveness was evaluated. Results A total of 20 545 155 person-times received human schistosomiasis examinations in Sichuan Province during the period from 2015 to 2023, and 232 157 person-times were seropositive, with a reduction in the seroprevalence from 2.10% (44 299/2 107 003) in 2015 to 1.12% (9 361/837 896) in 2023 (χ² = 7.68, P < 0.001). The seroprevalence of human schistosomiasis appeared a tendency towards a decline in Sichuan Province over years from 2015 to 2023 (b = −8.375, t = −10.052, P < 0.001); however, no egg positive individuals were identified during the period from 2018 to 2023, with the prevalence of human Schistosoma japonicum infections maintained at 0. Expanded chemotherapy was administered to 2 754 515 person-times, and medical assistance of advanced schistosomiasis was given to 6 436 persontimes, with the treatment coverage increasing from 46.80% (827/1 767) in 2015 to 64.87% (868/1 338) in 2023. Parasitological tests for livestock schistosomiasis were performed in 35 113 herd-times, and expanded chemotherapy was administered to 513 043 herd-times, while the number of fenced livestock decreased from 121 631 in 2015 to 103 489 in 2023, with a reduction of 14.92%. Snail survey covered 433 621.80 hm² in Sichuan Province from 2015 to 2023, with 204 602.81 hm² treated by chemical control and 4 637.74 hm² by environmental modifications. The area of snail habitats decreased from the peak of 5 029.80 hm² in 2016 to 3 709.72 hm² in 2023, and the actual area of snail habitats decreased from the peak of 8 585.48 hm² in 2016 to 473.09 hm² in 2023. The mean density of living snails remained low across the study period except in 2017 (0.62 snails/0.1 m²). Schistosomiasis control efforts by departments of agriculture and rural affairs in Sichuan Province included conversion of paddy fields to dry fields covering 153 346.93 hm², hardening of 6 110.31 km ditches, building of 70 356 biogas digesters, replacement of cattle with 227 161 sets of machines, and captive breeding of 21 161 070 livestock from 2015 to 2023, and the control efforts by departments of water resources included rivers and lakes management measuring 5 676.92 km and renovation of 2 331 irrigation areas, while the control efforts by departments of forestry and grassland included building of forests for snail control and schistosomiasis prevention covering 23 913.33 hm², renovation of snail control forests covering 8 720 hm² and newly building of shelterbelts covering 764 686.67 hm². All 63 endemic counties (cities and districts) had achieved the criterion for schistosomiasis elimination criteria in Sichuan Province by the end of 2023. Conclusion Following the integrated control efforts from 2015 to 2023, remarkable achievements have been obtained in the schistosomiasis control programme in Sichuan Province, with all endemic counties successfully attaining the schistosomiasis elimination target at the county level.

Objective To investigate the role of autophagy in contrast-induced acute kidney injury(CI-AKI)in rats and to explore its possible mechanism.Methods SD rats were randomly divided into control group,acute kid-ney injury model group(intravenous injection of contrast medium ioversol via tail vein;model),rapamycin(RAPA)group and hydroxychloroquine(HCQ)group.Blood urea nitrogen(BUN)and serum creatinine(Scr)con-tents were measured and the potential change foun in renal pathology was detected by HE staining and microscopy.Transmission electron microscopy was used to observe auto-phagy-related changes in ultrastructure.Western blot was used to observe the expression of microtubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3Ⅰ,ubiquitin-binding protein p62 and Histone deacetylase 4(HDAC4).The expression of HDAC4 was also observed by RT-qPCR.Results Compared with control group,the level of BUN,Scr and HDAC4 expression in the model and HCQ group was increased(P＜0.01),the proximal tubules of the kidney were significantly damaged.In the model group,auto-phagososomes and autolysosomes increased,accompanied by an increase of LC3Ⅱ/LC3Ⅰ and a decrease in the p62 level(P＜0.05,P＜0.01);Compared with model group,there were more autophagosomes and autolysosomes were found in RAPA group(P＜0.01),accompanied by increased LC3Ⅱ/LC3Ⅰratio and decrease in the p62 and HDAC4(P＜0.05,P＜0.01).In contrast,the number of autophagy related structures decreased in HCQ group(P＜0.01),accompanied by the simultaneous increase of LC3Ⅱ/LC3Ⅰ,p62 and the increase of HDAC4(P＜0.01).Conclusions Ioversol may induce autophagy activation,while enhancing autophagy by RAPA alleviates CI-AKI induced renal dysfunction.The mechanism is potentially atributed to the regulation of HDAC4.

Objective:To evaluate the qualitative and quantitative diagnostic value of transvaginal contrast-enhanced ultrasonography for benign and malignant adnexal masses.Methods:Forty-nine patients with adnexal masses detected by routine ultrasound examination at Wenzhou People's Hospital from January 2021 to December 2022 were included in this study. Initially, transvaginal two-dimensional ultrasound, two-dimensional ultrasound integrated with color Doppler, and contrast-enhanced ultrasonography were used to accurately classify the masses as benign or malignant. Using postoperative pathology as the gold standard, the qualitative diagnostic accuracy of various detection methods was compared. Subsequently, the receiver operating characteristic curve analysis was performed to assess the quantitative diagnostic accuracy of transvaginal contrast-enhanced ultrasonography-related parameters in distinguishing between benign and malignant adnexal masses.Results:Among the 49 patients, 10 were diagnosed with malignant tumors. The diagnostic accuracy of contrast-enhanced ultrasonography was 93.88% (46/49), with a sensitivity of 90.00% (9/10), a specificity of 94.87% (37/39), a positive predictive value of 81.82% (9/11), and a negative predictive value of 97.37% (37/38). The results of the diagnostic difference assessment (McNemar test) revealed that there was no significant difference between two-dimensional ultrasound ( χ2 = 0.37, P = 0.546), two-dimensional ultrasound combined with color Doppler ( χ2 = 0.17, P = 0.683), and contrast-enhanced ultrasonography ( χ2 = 0.00, P = 1.000), and the gold standard test results. The consistency assessment (Kappa test) revealed that the diagnostic results of contrast-enhanced ultrasonography exhibited the highest concordance with the gold standard, with a Kappa value of 0.82 ( P < 0.001). Furthermore, the receiver operating characteristic curve analysis indicated that the initial increase time, peak intensity, and mean transit time in contrast-enhanced ultrasonography demonstrated high quantitative diagnostic accuracy. The areas under the curve were 0.83, 0.82, and 0.84, respectively, and the diagnostic cutoff values were 17.30 s, 21.65 dB, and 92.60 seconds, respectively. Conclusion:Contrast-enhanced ultrasonography exhibits diagnostic value in the differential diagnosis of benign and malignant adnexal masses, both qualitatively and quantitatively. This method can provide valuable insights for further treatment.

Objective:To establish an HPLC fingerprint of Shenling Baizhu Powder and Shenling Baizhu Pills; To evaluate the quality consistency of commercial Shenling Baizhu Powder and Shenling Baizhu Pills.Methods:HPLC method was adopted with Agilent TC-C18 column (250 mm×4.6 mm, 5 μm). The mobile phase was 0.05% phosphoric acid-acetonitrile with gradient elution; the flow rate was 1.0 ml/min; the detection wavelength was 203 nm; the column temperature was 25 ℃. The HPLC fingerprints of Shenling Baizhu Powder and Shenling Baizhu Pills from different manufacturing enterprises were established and analyzed by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM (Version 2012) software for similarity evaluation, and the main chromatographic peaks were identified.Results:The control fingerprints of Shenling Baizhu Powder and Shenling Baizhu Pills were obtained. 73 common peaks and 79 common peaks were identified respectively. The similar degrees of all samples were over 0.92. The quality consistency of drugs different batches of different production enterprises was good. A total of 10 components were identified, including Liquiritin, Ginsenoside Rg1, Ginsenoside Rb1, Glycyrrhizin, Isoliquiritin, Ginsenoside Rd, Glycyrrhizic acid, AtractylenolideⅠ, AtractylenolideⅡ and AtractylenolideⅢ.Conclusions:The established HPLC fingerprints can quickly evaluate the formulation quality of Shenling Baizhu Powder and Shenling Baizhu Pills, providing basis the quality control.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of T-cell lymphoma. Despite the scarcity of reported BIA-ALCL cases in Asia, it is imperative to research early diagnosis. The crucial diagnostic criteria for BIA-ALCL include the presence of ALK - and CD30 + T cells exceeding 10% in the delayed seroma fluid. Furthermore, laboratory tests, such as histological examination of capsulectomies and analysis of clonal T-cell receptor (TCR) gene rearrangements, serve as important auxiliary diagnostic indicators. This article reported the case of a 56-year-old female patient who underwent bilateral breast augmentation with implants over 20 years ago. She presented with hardness, enlargement, and mild discomfort in her left breast. She was admitted to Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine in January 2023. MRI suggested implant rupture. Therefore, bilateral implant removal surgery was performed on February 2, 2023. Pathological examination of the fluid within the capsule of the left implant revealed a small number of ALK - and CD30 + T cells, with monoclonality observed in TCRγ gene rearrangement, indicating early changes suggestive of BIA-ALCL. Long-term follow-up is needed. The authors suggest that patients suspected of BIA-ALCL should undergo TCR gene rearrangement testing in addition to cytological and immunological examinations, which can provide guidance for the diagnosis, treatment, and necessary long-term follow-up of these patients.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

To summarize the nursing experience of a child with severe cardiopulmonary failure caused by fulminant myocarditis who underwent autologous vascular bypass grafting after severe lower limb ischemia during extracorporeal membrane oxygenation therapy.The key points of nursing include:①keeping the distal perfusion tube unobstructed before surgery to avoid aggravation of ischemia of the affected limb;physical precautions for deep vein thrombosis are strictly implemented to ensure the patency of the saphenous vein.②intraoperative nursing cooperation for the conversion of venous-arterial-venous extracorporeal membrane oxygenation to venous-venous extracorporeal membrane oxygenation.③on the premise of ensuring systemic perfusion after surgery,the blood pressure should be strictly controlled to prevent the rupture of the grafted vessel;to strengthen the management of coagulation to prevent bleeding and thrombosis;different position management of both lower limbs to keep the grafted blood vessels patency;to develop individualized exercise programs to enhance nutrition and promote rapid recovery;to give individualized psychological nursing care including childlike fun and sense of security,and eliminate children's negative emotions;to develop systematic health guidance and follow-up to improve the quality of family care for children.After treatment and nursing care,the postoperative grafted blood vessels were well anastomosed with no limb ischemia,and there was no swelling of the limb in the saphenous vein donor area.After 41 days of the treatment,the extracorporeal membrane oxygenation was withdrawn.The child recovered and discharged after 122 days;after 2 years of follow-up,the child could walk normally and recovered well.

Objective To explore the current situation and influencing factors of caregiver readiness of elderly patients with chronic heart failure.Methods From March 2021 to April 2022,the convenient sampling method was used to select 335 caregivers of elderly patients with chronic heart failure who were hospitalized in 6 hospitals in Hangzhou as the survey subjects.The general information questionnaire,Caregiver Readiness Scale and Caregiver Burden Scale were used to investigate the caregivers of elderly patients with chronic heart failure.Results A total of 326 valid questionnaires were collected.The score of Caregiver Readiness Scale for elderly patients with chronic heart failure was(18.88±6.36),and 61.04%of the caregivers had mild to moderate burden.The results of multiple linear regression analysis showed that the caregiver's age,education level and cumulative care time were the positive influencing factors of the caregiver readiness,and the caregiver burden was the negative influencing factor of the caregiver readiness(P＜0.001).Conclusion The caregiver readiness of elderly patients with chronic heart failure is at a medium level.Caregivers who are older,more educated,have a longer cumulative caregiving time,and have a lighter caregiving burden are more prepared.Medical staff should pay attention to the motivation of caregivers,provide professional support from multiple aspects,and reduce the burden of care,increase readiness level.