BACKGROUND:Swimming is an important non-pharmacological treatment for knee osteoarthritis,which can effectively alleviate the disease.However,the effect and mechanism of swimming on senile knee osteoarthritis are still unclear. OBJECTIVE:To investigate the effect of swimming exercise on the articular cartilage of aged mice with knee osteoarthritis. METHODS:Six 3-month-old male C57BL/6 mice were selected as the young group,and twelve 18-month-old male C57BL/6 mice were randomized into the aged group and the swimming group,with six mice in each group.Mice in the swimming group received adaptive swimming for 1 week and formal swimming for 8 weeks.After the intervention,stride length analysis and sampling were performed in each group.The total number of leukocytes and lymphocytes in peripheral blood was detected by blood routine examinations.The morphology of the articular cartilage was observed by hematoxylin-eosin and safranin O-fast green staining.Chondrocyte counts and the modified Mankin's score were used to evaluate the degree of articular cartilage damage.The protein and mRNA expressions of type Ⅱ collagen,aggrecan and matrix metalloproteinase 13 in articular cartilage were detected by immunohistochemical staining and RT-qPCR. RESULTS AND CONCLUSION:Compared with the young group,the mice in the aged group showed significantly decreased stride length(P＜0.05),significantly increased numbers of peripheral leukocytes and lymphocytes(P＜0.05),significantly decreased count of chondrocytes(P＜0.05),significantly increased modified Mankin's score(P＜0.05),significantly decreased protein and mRNA expression of type Ⅱ collagen and aggreca(P＜0.05),and significantly increased matrix metalloproteinase 13 expression(P＜0.05).Moreover,hematoxylin-eosin and safranin O-fast green staining showed the uneven surface of the articular cartilage,abnormal chondrocytes,and proteoglycan loss in the aged group.Compared with the aged group,swimming exercise significantly improved the stride length of mice(P＜0.05),decreased the count of peripheral blood lymphocytes(P＜0.05),increased the count of chondrocytes(P＜0.05),decreased the modified Mankin's score(P＜0.05),increased the protein and mRNA expression of type Ⅱ collagen and aggrecan(P＜0.05),and decreased the expression of matrix metalloproteinase 13(P＜0.05).Hematoxylin-eosin and safranin O-fast green staining showed that the articular surface of mice in the swimming group was smooth,chondrocytes were normal,and proteoglycan loss was less.All these findings indicate that swimming exercise can reduce the number of inflammatory cells in the blood of aged mice,improve articular chondrocytes,matrix composition and cartilage tissue morphology;thus,it has a protective effect on the cartilage of aged mice with knee osteoarthritis.

Objective To investigate the internal and external factors of scientific and technological innovations in pro-vincial maternal and child health care institutions and propose effective strategies for facilitating the innovations.Methods The PEST-SWOT model was used to analyze the internal strengths and weaknesses,external opportunities,and threats of the scientific and technological innovations in a provincial maternal and child health care institution from the perspectives of political,econom-ic,social,and technical environment.Results The institution has advantages and opportunities in policy support,scientific re-search management and investment,and disciplinary characteristics.However,it faces some threats and has disadvantages in tal-ent team,information-oriented level,and industrial competition.Conclusion The development of scientific and technological in-novation in provincial maternal and child health care institutions is affected by internal and external factors.It is necessary to firmly seize opportunities and comprehensively promote scientific and technological innovations from the aspects of medical treat-ment,teaching and research collaboration,discipline layout,talent team,and information-oriented construction.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

OBJECTIVE To investigate the effect of salidroside (Sal) on bone loss in obstructive sleep apnea syndrome(OSAS) rats by regulating the osteoprotegerin(OPG)/receptor activator of nuclear factor kappa-B ligand(RANKL) pathway. METHODS Rats were randomly divided into(12 rats/group) control group,OSAS group,Sal-L,Sal-M,and Sal-H groups(17.5,35,70 mg/kg). Except for the control group,all other groups were used to replicate the OSAS rat model through hypoxia and reoxygenation cycles. Bone density meters,three-point bending experiments,and Micro CT were applied to measure the bone density,biomechanics,and microstructural changes of the femur in rats. ELISA method was applied to detect serum levels of osteocalcin(BGP),alkaline phosphatase(ALP),and cross-linked carboxy-terminal telopeptide of type Ⅰ collagen(CTX-I). RT-PCR was applied to detect OPG and RANKL mRNA levels in the femur. Western blotting was applied to detect the expression of OPG/RANKL pathway proteins in the femur. RESULTS Compared with the control group,the bone density,maximum intensity,maximum load,trabecular bone volume fraction(Tb.BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the OSAS group were decreased,the mRNA and protein expression of CTX-I and RANKL were increased(P<0.05). Compared with the OSAS group,the bone density,maximum intensity,maximum load,Tb.BV/TV,Tb.N,Tb.Th,BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the Sal-L,Sal-M,and Sal-H groups were increased sequentially,the mRNA and protein expression of CTX-I and RANKL were decreased sequentially,the above changes were most great in the Sal-H group(P<0.05). CONCLUSION Salidroside promotes bone formation and inhibits bone resorption by increasing OPG expression and decreasing RANKL expression,thereby reducing bone loss in OSAS rats.

ObjectiveTo develop a deep learning system for early ultrasound screening of developmental dysplasia of the hip （DDH）， a new smart-hip ultrasound technique （S-hip）， and to validate its clinical application. MethodsWe selected 11，100 annotated and reviewed coronal ultrasound images of infant hips between November 2021 and August 2022， 8，100 of which were used for the training set and 3，000 for the test set， to build a S-hip deep learning system. To verify the consistency between the automated measurement by S-hip and the manual measurements by sonographers， 174 standard coronal ultrasound images of 87 infants' bilateral hips were acquired， then α angle， β angle and femoral head coverage （FHC） were measured by S-hip， an ultrasound expert and a resident. The measurement data and the time required for the measurements were recorded and statistically analyzed. Another 100 standard coronal ultrasound images of the hips were randomly selected and measured twice respectively by the ultrasound expert and resident to assess the intra-sonographer repeatability. ResultsThe intraclass correlation coefficient （ICC） （95% CI） values of α angle， β angle and FHC results measured by S-hip and ultrasound expert were 0.799 （0.738， 0.847）， 0.798 （0.737， 0.846） and 0.934 （0.954， 0.975）， respectively. Those values measured by the ultrasound expert and resident were 0.725 （0.645， 0.789）， 0.674 （0.583， 0.748） and 0.931 （0.908， 0.949）， respectively. The mean absolute errors （MAE） of α angle， β angle and FHC results between measurements by S-hip and ultrasound expert were 2.69 °， 4.43 ° and 2.47%， respectively. The time required for measurements by S-hip， ultrasound expert and resident was （1.59±0.36） s， （18.76±2.23） s and （19.45±2.76） s， respectively. The automated measurement by S-hip cost much shorter time than the manual measurements by sonographers and the difference was statistically significant （P<0.001）. The ICC （95% CI） values of α angle， β angle and FHC results between two measurements by the ultrasound expert were 0.943 （0.916， 0.961）， 0.959 （0.940， 0.972）， and 0.981 （0.971， 0.987）， respectively. Those values by the ultrasound resident were 0.884 （0.833， 0.921）， 0.921 （0.884， 0.946）， and 0.962 （0.944， 0.974）. ConclusionThe S-hip based on a deep learning system is a highly reliable automated technique to accurately measure α angle， β angle and FHC. Compared with ultrasound residents， S-hip allows for a more simplified and significantly quicker measurement， which may enhance the widespread use of hip ultrasound screening in infants.

The total number of cancer patients who are eligible for and will benefit from immune checkpoint inhibitors (ICIs) in China has not been quantified. This cross-sectional study was conducted to estimate the number of Chinese cancer patients with eligibility and response to ICIs based on the 2015 Chinese cancer statistics and the immune checkpoint inhibitor clinical practice guideline of the Chinese Society of Clinical Oncology. A total of 11 ICIs were recommended for 17 cancer types. The estimated number of eligible patients annually was 1 290 156 (55.18%), which included 888 738 males (60.05%) and 400 468 females (46.67%). The estimated number of responders annually was 448 972 (19.20%), which included 309 023 males (20.88%) and 139 764 females (16.29%). Gastric cancer (n=291 000, 12.45%), non-small-cell lung cancer (n=289 629, 12.39%), and hepatocellular carcinoma (n=277 100, 11.85%) were the top three cancer types with the highest number of eligible patients. Non-small-cell lung cancer (n=180 022, 7.70%), hepatocellular carcinoma (n=75 648, 3.24%), and small-cell lung cancer (n=64 362, 2.75%) were the top three cancer types with the highest number of responders. In conclusion, ICIs provide considerable benefit in Chinese cancer patients under optimal estimation.
Humans ; Male ; Female ; Carcinoma, Non-Small-Cell Lung/pathology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/drug therapy* ; Antineoplastic Agents, Immunological/therapeutic use* ; Cross-Sectional Studies ; Carcinoma, Hepatocellular ; Liver Neoplasms

Objective:To investigate the relationship between the expression of serum exsomal miRNA-155-5p (miR-155-5p) and prognosis in patients with esophageal squamous cell carcinoma (ESCC).Methods:A total of 336 samples from ESCC patients in Fujian Provincial Cancer Hospital from October 2014 to December 2015 were collected. The relative expression levels of serum exsomal miR-155-5p were detected by using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). Cut-off value of the expression levels of serum exsomal miR-155-5p was determined by using X-tile software. Based on the optimal cut-off value, patients were divided into miR-155-5p low expression group and miR-155-5p high expression group. The survival curve was drawn by using Kaplan-Meier method and Cox proportional hazards regression model was used to make survival analysis.Results:The cut-off value of serum exsomal miR-155-5p expression level was 2.340. According to the cut-off value, patients were divided into miR-155-5p low expression group (<2.340) of 51 cases and miR-155-5p high expression group (≥2.340) of 285 cases. There were no statistical differences in age ( χ2 = 0.020, P = 0.887), gender ( χ2 = 0.283, P = 0.595), tumor location ( χ2 = 0.063, P = 0.977), differentiation grade ( P = 0.474), clinical staging ( χ2 = 3.996, P = 0.136) and surgery treatment ( χ2 = 0.941, P = 0.332) of patients in both groups. ESCC patients in serum exsomal miR-155-5p high expression had a higher risk of death compared with patients in miR-155-5p low expression group ( HR = 1.763, 95% CI 1.049-2.961, P = 0.032). Conclusion:The high expression level of serum exsomal miR-155-5p is associated with poor prognosis in ESCC patients and it could be used as a prognostic new marker in ESCC patients.

Objective:To deeply understand needs and problems of on-site nursing service training for "network nurses", so as to provide a reference for the construction of "Internet + Nursing Service" training content system standards.Methods:Using the purposive sampling method and based on principle of maximum differentiation, a total of 12 "network nurses" in Ningbo were selected from March to May in 2020 to conduct semi-structured interviews. Braun thematic analysis method was used to analyze data and extract themes.Results:A total of 4 themes were obtained. The first was that the requirements of practicing safety education and training included risk prevention training, adverse event handling process training, emergency response plans and complication handling training. The second was the needs of humanistic care education and training, including on-site service language, code of conduct training, nurse-patient communication training and health education knowledge training. The third was the demand for diversified training forms. Fourthly, factors affecting training quality.Conclusions:"Network nurses" have a greater demand for occupational safety education and humanistic care education. It is recommended that multiple parties should cooperate to improve the "Internet +Nursing Service" emergency laws and regulations as soon as possible, provide diversified training models, reserve high-quality "Internet + Nursing Service" talents and promote continuous and standardized development of "Internet + Nursing Service".

Objective:To develop a novel α vβ 3-targeted theranostic agent 177Lu-Evans blue (EB)-Arg-Gly-Asp (RGD) and evaluate its value for SPECT imaging and targeted radionuclide therapy in the non-small cell lung cancer (NSCLC)-patient-derived xenografts (PDX). Methods:The α vβ 3-targeted molecule RGD was conjugated with the albumin binding moiety EB to obtain EB-RGD, and EB-RGD was further conjugated with the chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) for 177Lu radiolabeling. NSCLC-PDX mice models ( n=68) were established. 177Lu-EB-RGD SPECT imaging, biodistribution study were performed in 28 PDX mice models after being injected with 177Lu-EB-RGD or 177Lu-RGD. Targeted radionuclide therapy were subsequently performed in NSCLC-PDX mice models, saline group (group A), 18.5 MBq 177Lu-RGD group (group B), 18.5 MBq 177Lu-EB-RGD group (group C), 29.6 MBq 177Lu-EB-RGD group (group D), n=10 in each group; tumor volumes of PDX mice models in each group were observed within 50 d. Differences between 2 groups were compared using independent-sample t test. Results:177Lu-EB-RGD was radiolabeled at a specific activity of (55±14) GBq/μmol, with a radiochemical yield of more than 95% and a radiochemical purity of more than 95%. Regarding the SPECT imaging, tumors in NSCLC-PDX mice were clearly observed from 4 to 96 h post-injection and the tumor to muscle ratio (T/M) reached 7.34±0.67, 14.63±3.82, 15.69±3.58 and 15.99±5.42 at 4, 24, 72, 96 h post-injection, respectively. Biodistribution study further confirmed the findings from SPECT imaging, and the tumor uptake of 177Lu-EB-RGD were markedly increased compared to 177Lu-RGD 4 h post-injection ((10.15±1.17) vs (3.30±1.47) percent injection dose per gram (%ID/g); t=18.60, P<0.05). Regarding targeted radiotherapy, the tumor volumes were quickly increased within 50 d after treatment in group A and B, while the tumor volumes were decreased in group C and D, until the tumors in group C and D disappeared at the 28th day after initial treatment with no sign of recurrence during the observation period. Conclusions:177Lu-EB-RGD can target α vβ 3-positive NSCLC-PDX with intense tumor to background ratio and strong tumor inhibition efficacy. The preclinical data suggests that 177Lu-EB-RGD may be an effective new treatment option for advanced NSCLC patients with resistance or ineffective results for targeted therapy.

Objective:To investigate the therapeutic efficacy and potential mechanisms of integrin α vβ 3-targeted radionuclide therapy (TRT) in combination with anti-programmed cell death protein ligand 1 (PD-L1) immunotherapy. Methods:Integrin α vβ 3-targeted molecule Arg-Gly-Asp (RGD) was conjugated with Evans blue (EB) and then labeled with 177Lu to obtain 177Lu-EB-RGD. The radioactivity and radiochemical purity were determined. MicroSPECT imaging, biodistribution, and in vivo therapeutic efficacy were subsequently performed in MC38 murine colon cancer models. Volume of tumor and body mass of mice were observed to assess the therapeutic efficacy and safety ( n=9 in each group). Flow cytometry was used to evaluate therapy response of saline-treated (control, group A), 18.5 MBq 177Lu-EB-RGD-treated (group B), 10 mg/kg PD-L1 antibody-treated (group C), TRT combined with immunotherapy-treated (group D, 18.5 MBq 177Lu-EB-RGD and 10 mg/kg PD-L1 antibody) mice and alterations in tumor microenvironment (PD-L1 + immune cells, CD8 + T cells and regulatory T cells). Independent-sample t test and repeated measures analysis of variance were used for data analysis. Results:The radioactivity of 177Lu-EB-RGD was (55.85±14.00) GBq/μmol. SPECT imaging clearly visualized the MC38 tumors in mice models with high uptake and long retention time, the tumor/muscle ratio reached 14.87±0.88 at 24 h postinjection, while less uptake and retention in normal tissues. Tumor uptake of 177Lu-EB-RGD was significantly higher than that of 177Lu-RGD 4 h post-injection ((12.00±1.60) vs (3.69±0.37) %ID/g; t=8.63, P<0.01). The efficacy results between each treatment group was significantly different ( F=7.32, P=0.03) at day 6 post-treatment. The combination therapy showed the most outstanding anti-tumor efficacy with 7/9 mice showed complete response. Flow cytometry results showed that TRT up-regulated the PD-L1 expression significantly, namely, PD-L1 + immune cells in group B and group A were significantly different (CD45 + /PD-L1: 2.34% vs 0.95%, CD11b + /PD-L1: 2.41% vs 0.66%; t values: 11.17 and 8.70, both P<0.01); immunotherapy and combination therapy dramatically stimulated the infiltration of CD8 + T cells (2.07% vs 0.26%, 2.71% vs 0.26%; t values: 4.10 and 6.03, both P<0.05). Conclusion:TRT in combination with immunotherapy synergistically enhance anti-tumor efficacy, which is expected to play a role in the treatment of patients with advanced tumor where TRT can be applied.