Objective: To identify the social ecological factors of individual, family, and physical environments for affecting the development of fundamental motor skills (FMS) among overweight and obese children, so as to provide a basis for the future intervention design and policy making. Methods: From March to April 2022, one public primary school was recruited from each of the 4 main urban areas in Shijiazhuang, and a total of 425 children in schools were recruited for data collection including individual, family, physical environmental factors, by using a stratified cluster random sampling approach. Test of Gross Motor Development-Third Edition (TGMD-3) was used to evaluate children s FMS. Hierarchical linear regression model was employed to analysis the associations between the 18 factors for individual, family, and physical environments, and the FMS of overweight and obese children. Results: Individual level including the child s age, gender and sleep duration, and family level including high family economic level, parental support for physical activity, and the physical activity environment surrounding the family and community were consistent predictors of movement skills ( B =0.422, -1.972, 0.014, 0.045, 1.042, 0.827, 1.898), ball skills ( B =0.858, 3.953, 0.013, 0.092, 2.141, 1.173, 1.954), and composite skills ( B =1.305, 1.915, 0.028, 0.142, 3.091, 1.962, 3.879) among overweight and obese children ( P <0.05). Furthermore, child s body mass index (BMI), moderate to vigorous physical activity, perceived motor competence, pleasure of exercise,as well as BMI and physical activity levels of their primary caregiver, were associated with different types of FMS ( P <0.05). Individual, family, and physical environmental factors had moderate to high predictive explanatory power for FMS among overweight and obese children ( 2=0.69, 0.75, 0.93, P <0.01). Conclusions The factors influencing the development of FMS in overweight and obese children are multifaceted, with individual, family, and physical environment factors all playing significant roles.Corresponding measures should be actively taken to improve FMS in overweight and obese children.

Gynecologic malignant tumors are among the leading diseases threatening women's lives and health,with the highest morbidity and mortality rates among all female diseases.These tumors originate from female reproductive organs and are typically classified based on the affected site.Ovarian cancer(OC),endometrial cancer(EC)and cervical cancer(CCA)are the most common types.Currently,gynecologic malignant tumors are primarily treated with a combination of surgery,chemotherapy and radiotherapy,where drugs play a critical role in the treatment process.However,the actual clinical effectiveness is often influenced by various factors,such as adverse reactions due to drug toxicity and the drug resistance and insensitivity observed in some patients,which limit improvements in patient survival rates.Recent studies have shown that the same type of tumor exhibits significant biological characteristics and drug response heterogeneity among different individuals,which is a key factor contributing to the varied clinical outcomes when using the same drug treatment for the same type of gynecologic malignant tumor.To achieve individualized and precise treatment for gynecologic malignant tumors,there is an urgent need to develop in vitro models that closely resemble human tumors for clinical research.Drug screening is a technique used to identify and evaluate compounds with pharmacological activity and potential therapeutic effects,providing doctors with scientific guidance on drug use,thereby avoiding blind drug testing and reducing patients'therapeutic pain and economic burden by assessing the effects of different drugs under specific conditions.Organoid models have been extensively studied as an innovative drug screening tool and personalized medicine for treating gynecologic malignancies.Organoids are tissue-like structures with a specific spatial arrangement formed in vitro through three-dimensional cell culture,capable of highly simulating the structure and function of tissues in vivo and displaying histological and genotypic characteristics very similar to human organs.This approach has largely overcome the limitations of traditional tumor models,such as patient-derived cancer cell models and patient-derived tumor xenograft models,becoming an essential research tool in oncology.It provides a more physiologically relevant experimental platform for drug screening studies of gynecologic malignancies.This paper compared the advantages and disadvantages of several preclinical cancer models,reviewed the development process of organoids,and described the establishment of gynecologic oncology organoids and their application in drug screening for ovarian,endometrial,and cervical cancers.Additionally,we discussed the current limitations of organoid technology in its application and envisioned its future development,aiming to provide insights for future medical research,particularly in new drug discovery and personalized medicine.

Human epidermal growth factor receptor 2 (HER2), programmed death-1 and programmed death-ligand 1 are related to the proliferation, invasion and metastasis of various tumor cells. A variety of antibodies and small molecule drugs targeting HER2 have achieved considerable results in clinical practice. Immune checkpoint inhibitors targeting programmed death-1 and programmed death-ligand 1 have significant effects in clinical application. In the KEYNOTE-811 trial, the combination of immune checkpoint inhibitors and targeted therapy has achieved encouraging results in HER2-positive advanced gastric cancer.

Objective To assess the comparative efficacy of different methods for difficult biliary cannulation in endoscopic retrograde cholangio-pancreatography(ERCP)through a network meta-analysis.Methods Randomized controlled trials(RCTs)that compared the efficacy of different adjunctive methods(early or late needle-knife technique,pancreatic guidewire-assisted technique,pancreatic stent-assisted technique,transpancreatic sphincterotomy,persistent standard cannulation technique)for difficult biliary cannulation with each other were identified.The success rate of biliary cannulation and the incidence of post-ERCP pancreatitis(PEP)were the outcomes of interest.Pairwise and network meta-analysis and ranking according to surface under the cumulative ranking curve(SUCRA)for all methods were performed.Results Eighteen RCTs were identified according to selection criteria,and 2 033 patients were enrolled.The use of transpancreatic sphincterotomy over persistent standard cannulation technique(RR=1.34,95%CI:1.02-1.77)and over pancreatic guidewire-assisted technique(RR=1.26,95%CI:1.00-1.60)significantly increased the success rate of biliary cannulation.Based on SUCRA ranking,transpancreatic sphincterotomy followed by early needle-knife techniques were ranked highest in terms of increasing the success rate of biliary cannulation.Only early needle-knife technique significantly decreased PEP rate when compared with persistent standard cannulation technique(RR=0.53,95%CI:0.30-0.94),whereas both early needle-knife techniques and transpancreatic sphincterotomy led to lower PEP rates as compared with pancreatic guidewire-assisted technique(RR=0.41,95%CI:0.17-0.99;RR=0.49,95%CI:0.25-0.96;respectively).Based on SUCRA ranking,early needle-knife technique followed by transpancreatic sphincterotomy were ranked highest for decreasing the PEP rate of biliary cannulation.Conclusions Transpancreatic sphincterotomy increases the success rate of difficult biliary cannulation in ERCP;early needle-knife technique and transpancreatic sphincterotomy are superior to other interventions in decreasing PEP rates and should be considered as a choice of difficult biliary cannulation.

The miR-34 family plays an important role in gastric cancer, and the inactivation or reduced expression of the miR-34 family is detected in gastric cancer cell lines and gastric cancer tissues compared with normal gastric mucosa tissues, indicating it is associated with the occurrence and development of gastric cancer. Studies have shown that miR-34 plays a key role in inhibiting gastric cancer progression by regulating IGF2BP3, survivin, Bcl-2 and epithelial-mesenchymal transition-related pathway, indicating that miR-34 is an important target for gastric cancer treatment. In terms of clinical treatment, miR-34 has not only been proved to have radiochemotherapy sensitization, but also achieved good curative effect in tumor clinical trials. With the emergence of miR-34 vectors targeting gastric cancer, it is possible to use it for gastric cancer treatment. Deep understanding of the molecular basis and clinical efficacy of miR-34 for gastric cancer treatment can help to evaluate the potential of the miR-34 family as a new therapeutic target for gastric cancer.

Objective:To investigate the effects of programmed death-ligand 1 (PD-L1) expression on the biological behaviors of gastric cancer cell line MKN45.Methods:The PD-L1 gene of gastric cancer cell line MKN45 was silenced by RNA interference technique. MKN45 cells were divided into blank control group, si-NC group (transfected with siRNA-NC) and si-PD-L1 group (transfected with siRNA-PD-L1). Quantitative real-time PCR was used to detect the mRNA expressions of PD-L1 and epithelial-mesenchymal transformation (EMT)-related proteins E-cadherin, Vimentin and Snail in MKN45 cells, and Western blotting was used to detect the expression levels of PD-L1 protein in MKN45 cells of each group. Transwell migration test, Transwell invasion test and MTT test were used to detect the migration, invasion and adhesion abilities of MKN45 cells.Results:The relative expression levels of PD-L1 mRNA in the blank control group, si-NC group and si-PD-L1 group were 1.002±0.092, 1.005±0.121 and 0.237±0.017, respectively, with a statistically significant difference ( F=75.61, P<0.001). The protein expression levels of PD-L1 in the three groups were 0.944±0.028, 1.008±0.088 and 0.269±0.015, respectively, with a statistically significant difference ( F=172.99, P<0.001). The mRNA and protein expression levels of PD-L1 in the si-PD-L1 group were lower than those in the other two groups (all P<0.001), but there were no statistically significant differences between the blank control group and si-NC group (all P>0.05). The cell migration rates of the blank control group, si-NC group and si-PD-L1 group were (1.000±0.020)%, (1.012±0.084)% and (0.488±0.050)%, respectively, with a statistically significant difference ( F=80.73, P<0.001). The cell invasion rates of the three groups were (0.929±0.087)%, (0.924±0.208)% and (0.300±0.100)%, respectively, with a statistically significant difference ( F=19.37, P<0.001), and the cell adhesion rates of the three groups were (100.000±5.407)%, (99.280±4.845)% and (59.723±2.674)%, respectively, with a statistically significant difference ( F=79.87, P<0.001). Compared with the blank control group and si-NC group, the migration, invasion and adhesion abilities of MKN45 cells in the si-PD-L1 group decreased significantly (all P<0.001). The expression levels of E-cadherin mRNA of the three groups were 1.000±0.023, 0.981±0.051, 3.618±0.201, the expression levels of Vimentin mRNA were 1.000±0.043, 1.108±0.150, 0.328±0.011, the expression levels of Snail mRNA were 1.061±0.103, 1.090±0.110, 0.304±0.043, respectively, with statistically significant differences ( F=477.17, P<0.001; F=65.97, P<0.001; F=72.70, P<0.001). Compared with the blank control group and si-NC group, the mRNA expression levels of Vimentin and Snail of MKN45 cells in the si-PD-L1 group decreased, while the expression level of E-cadherin mRNA increased, with statistically significant differences (all P<0.001). Conclusion:Silencing the expression of PD-L1 can reduce the migration, invasion and adhesion abilities of MKN45 cells, and the mechanism may be related to the effect of PD-L1 on the EMT pathway of gastric cancer.

Objective:To investigate the characteristics and causes of endplate injury in the oblique lateral interbody fusion for the treatment of lumbar diseases, and summarize the precaution of endplate injury.Methods:Thirty-five cases of endplate injury were observed, which were originally treated with oblique lateral interbody fusion with or without pedicle screw fixation from October 2014 to December 2017. There were 7 males and 28 females, and the age ranged from 51 to 78 years old (averagely 62.8±8.13 years). There were 2 cases of lumbar disc degeneration, 10 cases of lumbar canal stenosis, 17 cases of lumbar degenerative spondylolisthesis, 2 cases of lumbar spondylolysis with or without spondylolisthesis, and 4 cases of lumbar degenerative scoliosis. Lesion sites contained L 3,4 in 2 cases, L 4,5 in 21 cases, L 2-4 in 3 cases, L 3-5 in 4 cases, L 2-5 in 3 cases and L 1-5 in 2 cases. Preoperative bone mineral density examination revealed there were 7 cases of T>-1 SD, 24 cases of -2.5 SD

Objective To observe the differential expression of high mobility group box - 1 protein (HMGB1) in renal tissues of heat stroke mice models, and to explore its role in the pathogenesis of heat stroke associated acute kidney injury(HS-associated AKI). Methods According to random number table, 20 healthy male C57BL/6J mice were randomly divided into 2 groups, including normal control (n=10) and heat stroke group (n=10). The mice in heat stroke group were given with a 2-hour-exposure in biological simulation chamber (temperature 41℃, humidity 70％). Heat stroke was defined as anal temperature lasting more than 40 degrees Celsius. A 18F - deoxyglucose nuclide labeled vivo imaging was conducted with micro - positron emission tomography(PET)/computer tomography (CT). Serum creatinine was examined with blood example. In order to evaluate the pathological changes, HE stain was conducted with kidney tissue, and mitochondrial morphological changes in kidney tissue were observed by transmission electron microscopy. The expressions of HMGB1 and apoptosis inducing factor mitochondria associated 2 (Aifm2) were examined by immunohistochemical method, and the levels of HMGB1 and RAGE were examined by Western blotting. The cell apoptosis of renal tissue was detected by terminal deoxynucleotidyl transferase -mediated dUTP - biotin nick end labeling assay (TUNEL). The metabolomics of kidney tissue in mice were detected by liquid chromatography - mass spectrometry (LC - MS), and the pathway enrichment analysis was carried out by KEEG database. Results (1) The body temperature of the mice in heat shock group was significantly higher than that in normal control group 45 min after model establishment (P＜0.05). The level of serum creatinine in heat shock group was significantly higher than that in normal control group (P＜0.05), and the levels of 18F - deoxyglucose increased in skeletal muscle and visceral tissue of the mice in heat - shock group. (2) HE staining showed hemorrhage in collecting duct and tubular endothelial cell swelling, and mitochondrial swelling and deformation were observed by transmission electron microscopy in kidney tissue of the heat shock group. (3) Immunohistochemical method showed that the levels of Aifm2 and HMGB1 in heat shock group were higher (P＜0.05). (4) Western blotting showed that the levels of HMGB1 and RAGE in heat shock group were higher than those in normal control group (P＜0.05). (5) TUNEL showed that the number of cells with positive stain in kidney tissue of the heat shock group was higher than that in normal control group (P＜0.05). (6) Between normal control group and heat shock group, 136 differential metabolites were detected in kidney tissues. After analysis by KEGG database, pathway abnormalities such as unsaturated fatty acid metabolism disorder may be associated with HS - associated AKI, and many differential metabolites such as adrenic acid may be important regulatory points in the pathogenesis. Conclusion Acute kidney injury is a common complication of heat shock. It may be related to the dysfunction of renal mitochondria and activation of apoptotic pathway caused by systemic hypercatabolism, which may be related to the disorder of unsaturated fatty acid metabolism and activation of HMGB1. Some differential metabolites may be of high value in HS- associated AKI studies.

Objective To observe the efficacy of oropharyngeal muscle exercise for relieving obstructive sleep apnea (OSAS) among stroke survivors.Methods Fifty stroke survivors with moderate OSAS were randomly divided into an observation group and a control group,each of 25.Both groups were given routine drugs and rehabilitation,while the observation group was additionally provided with oropharyngeal muscle exercises during the daytime for 20 minutes twice a day for6 weeks.The control group received deep breathing therapy.Before and after the 6 weeks of treatment,both groups were evaluated using polysomnography.Their sleep quality and daytime sleepiness were measured using the Pittsburgh sleep quality index and the Stanford sleepiness scale.Any changes in the patients' pharyngeal morphology after exercise were evaluated using MRI.Results After the oropharyngeal muscle exercises,the apnea hypoventilation index and minimum SaO2 ％,the snore index and sleep quality improved significantly.Daytime sleepiness was significantly relieved.Some structural remodeling of the pharyngeal airvay was observed by MRI,including significantly larger retropalatal distance and shorter length of the soft palate.The retropalatal distance was positively and correlated with the duration of exercise while the length of soft palate correlated negatively.Conclusion Exercising the oropharyngeal muscles is a promising alternative treatment for stroke survivors with moderate OSAS.It improves the morphology of the oropharynx to relieve obstruction during sleeping.

Objective To investigate the correlation between tumor-associated macrophages (TAMs) and the development of high risk human papilloma virus (hr-HPV)-related cervical cancer. Methods A total of 112 cases of cervical tissue were collected, including 16 normal cervical tissues, 55 cervical intraepithelial neoplasia (CIN) tissues and 41 squamous cervical cancer (SCC) tissues. The expression of CD163+ macrophages in the cervical tissues was detected by immunohistochemical method, and the results were analyzed in relation with the clinical data of the patients. Results Immunohistochemical analysis showed that the cell density of CD163+macrophages increased progressively with the increase in the tissue malignancy, in the order of normal cervical tissue, CIN I, CIN II-III, and SCC. Correlation analysis revealed a positive relationship between CD163 + macrophage density and tissue malignancy (P=0.000). The density of CD163 + macrophages was significantly upregulated in HR-HPV-positive SCC tissue (P<0.05). CD163+ macrophages were positively correlated with cervical lymph node metastasis (P=0.005) and FIGO stage (P=0.004) of SCC. Conclusion The expression of CD163+macrophages is positively correlated with malignant transformation of cervical tissues, and hr-HPV infection is significantly correlated with CD163 expression level in the macrophages. CD163+ macrophages can be used as predictors of the occurrence and progression of cervical cancer caused by hr-HPV infection.