ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To investigate the therapeutic effect difference between first-line treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) and chemotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) rare mutation.Methods:A retrospective case-control study was performed. Data of NSCLC patients with rare EGFR mutation who were treated in Shanxi Province Cancer Hospital from January 2013 to October 2019 were retrospectively analyzed. EGFR mutations in living tissues or blood were detected by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) before first-line treatment. According to first-line treatment methods,they were divided into EGFR-TKI treatment group and chemotherapy group. Objective remission rate (ORR) and disease control rate (DCR) of both groups were compared. Kaplan-Meier method was used to draw progression-free survival (PFS) and the overall survival (OS) curves. Log-rank test was used for comparison among groups. Single-factor and multi-factor Cox proportional risk models were used to analyze the influencing factors of PFS and OS.Results:A total of 169 patients with EGFR rare mutations were included, and the age [ M (IQR)] was 63 years (12 years); there were 96 cases (56.8%) < 65 years and 73 cases (43.2%) ≥65 years; 70 (41.4%)males and 99 (58.6%) females; 55 cases (32.5%) had EGFR G719X mutation,45 cases (26.6%) had L861Q mutation, 17 cases (10.1%) had S768I mutation, and 52 cases (30.8%) had complex mutation; 55 cases (32.5%) received the first-line chemotherapy and 114 cases (67.5%) received the first-line EGFR-TKI treatment. In the chemotherapy group, ORR was 36.4% (20/55) and DCR was 85.5% (47/55); in EGFR-TKI treatment group, ORR was 72.8% (83/114) and DCR was 90.4% (103/114). The ORR of EGFR-TKI treatment group was higher than that of chemotherapy group ( χ2 = 20.70, P = 0.001), and there was no statistically significant difference in DCR between two groups ( χ2 = 1.76, P = 0.184). Subgroup analysis showed that ORR in EGFR-TKI treatment group with G719X, L861Q and complex mutations was higher than that of the corresponding mutations in chemotherapy group, and the differences were statistically significant (all P < 0.05), while there were no significant differences in DCR among subgroups (all P > 0.05). The median PFS time was 9.7 months (95% CI: 6.0-13.4 months) and 3.8 months (95% CI: 3.1-7.1 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was a statistically significant difference in PFS between the two groups ( P < 0.001). The median OS time was 25.6 months (95% CI: 18.0-37.9 months) and 31.7 months (95% CI: 18.0-42.8 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was no statistically significant difference in OS between the two groups ( P = 0.231). Multivariate Cox regression analysis showed that brain metastasis [with vs. without: HR = 2.306, 95% CI: 1.452-3.661, P < 0.001] and the first-line treatment methods (EGFR-TKI vs. chemotherapy: HR = 0.457, 95% CI:0.317-0.658, P < 0.001) were independent influencing factors for PFS of NSCLC patients with EGFR rare mutation; brain metastasis (with vs. without: HR = 2.087, 95% CI: 1.102-3.953, P = 0.024; unknown vs. without: HR = 2.118,95% CI: 1.274-3.520, P = 0.004) were independent influencing factors for OS of NSCLC patients with EGFR rare mutation. Conclusions:Compared with the first-line chemotherapy, EGFR-TKI first-line treatment could improve objective remission and PFS of NSCLC patients with EGFR rare mutation, while no OS benefit is observed.

Objective:To explore the anxiety level, influencing factors among surrogate decision-makers of patients with acute ischemic stroke during thrombolysis decision-making, and their correlation with decision-making duration.Methods:Acute ischemic stroke patients and their surrogate decision-makers who visited the Emergency Department of the First Affiliated Hospital of Zhengzhou University from September 2019 to December 2021 were selected as the research subjects.Sociodemographic data and disease related data of patients and surrogate decision-makers were collected.Surrogate decision-makers were evaluated with the state-trait anxiety inventory, decision participation expectation scale, Wake Forest physician trust scale, and perceived social support scale.SPSS 26.0 software was used for data processing.Pearson correlation analysis, Spearman correlation analysis and ridge regression analysis were used for statistical analysis.Results:The score of state anxiety of decision-makers was (49.47±9.04), and 18.2% (70/383) of decision-makers had a decision duration exceeding 15 minutes.The score of state anxiety of decision-makers was positively correlated with decision duration ( r=0.189, P<0.001). The influencing factors of state anxiety level of decision-makers included sociodemographic factors (age of decision-makers and patients, relationship between payers and patients, whether decision-makers bear the current medical expenses, type of medical insurance for patients), psychological factors (trust level in physicians, perceived social support), factors related to patient disease (numbers of stroke relapses, National Institutes of Health stroke scale scores for patients), characteristics of the decision-making process (whether patients participate in the decision-making process, and the role of decision-makers in the decision-making process) (all P<0.05). Conclusion:Most surrogate decision-makers experience anxiety.Medical staff should pay attention to the emotions of decision-makers and adopt appropriate communication skills when communicating with informed consent for thrombolysis, alleviate the anxiety of surrogate decision-makers, so as so reduce the decision-making duration.

Objective To investigate the feasibility of using contrast-enhanced T1WI radiomics in predicting the pathological grade in rectal adenocarcinoma.Methods The MRI and pathological data of 127 patients with rectal adenocarcinoma were analyzed retrospectively.ITK-SNAP software was used to manually draw region of interest(ROI)in rectal cancer on axial T,WI enhanced images.The radiomics features were extracted by the Pyradiomics software from ROI.The task was divided into two parts:task 1("high & non-high"group)predicted the high-differentiation and moderate/low-differentiation of the tumor;task 2("moderate & low"group)predicted the tumor's moderate-differentiation and low-differentiation in"non-high"group.Maximum relevance and minimum redundancy(mRMR)method was used to screen features.The five methods including least absolute shrinkage and selection operator(LASSO),logistic regression(LR),naive Bayes(NB),random forest(RF),and support vector machine(SVM)were used to build the models,and the efficiency of each model was evaluated and compared.Results In task 1,the area under the curve(AUC)of five methods were 0.86,0.90,0.59,1.00,0.99 in the training cohort and 0.71,0.62,0.53,0.67,0.64 in the testing cohort.In task 2,the AUC of five methods in the training cohort were 0.93,0.85,0.67,0.92,0.89,and in the testing cohort were 0.86,0.80,0.50,0.78,0.71.The models constructed by LASSO in both tasks were the dominant models,the AUC of the fusion model in the testing cohort which combined with age,gender and the dominant Radiomics score(Radscore)was 0.80[95％confidence interval(CI)0.63-0.96]in task 1,and the accuracy,sensitivity and specificity were 78.94％,77.78％,and 79.31％respectively.They were 0.89(95％CI 0.74-1.00),90.00％,95.65％,and 71.43％,respectively in task 2.The calibration curves showed that the fusion models had a good goodness of fit.Conclusion Based on the establishment of two dichotomous models,the radiomics based on the contrast-enhanced T1 WI is feasible in predicting the high,moderate and low differentiation degree of rectal adenocarcinoma.

Hemichorea associated with non-ketotic hyperglycemia(HC-NH)is a rare complication of diabetes mellitus. It is characterized by sudden and spontaneous non-repeating movements. Clinically, it presents as irregular dance-like movements in the distal parts of one limb, with unilateral involvement being more common and bilateral involvement being rare. Early diagnosis and treatment could improve the prognosis. We report a patient with hyperglycemia who developed bilateral involvement. It highlights the need to consider this condition in diabetic patients who present with secondary involuntary limb movements. Early treatment may lead to reversal of the symptoms.

Objective:To explore the manifestations of magnetic resonance imaging(MRI)on acute traumatic lateral patellar dislocation of children and adolescents.Methods:MRI images of the affected side and healthy side of 110 children and adolescents with acute traumatic lateral patellar dislocation who were treated in the Second Hospital of Tangshan from July 2016 to April 2022 were retrospectively analyzed.The correlation of the medial patellofemoral ligament(MPFL)on the affected side between the tear location and tear degree was compared and analyzed.According to the cartilage injury grading system of international cartilage repair society(ICRS),the articular cartilage injury of affected side was divided into 4 grades,and the correlation between the articular cartilage injury grading and the articular cartilage injury location was compared and analyzed.Three methods of measuring patellar height,which included Insall-Salvati index(ISI),patellotrocheal index(PTI)and Caton-Deschamps index(CDI),were used to compare and analyze the differences of MRI data of patellar height between the affected side of knee joint and the healthy knee joint of pediatric children.Results:In 110 patients with MPFL injury,73 cases were partial tears and 37 cases were complete tears.There was significant difference in the injury at MPFL patellar attachment location between complete tears(22 cases)and partial tears(19 cases)(x2=11.740,P<0.05),and there was significant difference in MPFL multiple injury between partial tear(40 cases)and complete tear(8 cases)(x2=10.990,P<0.05).There were no significant differences in the injuries of MPFL middle segment and the origin of femur between partial tears and complete tears.There were 162 lesions in 110 cases with osteochondral injury,which included 55 lesions on the patellar side,33 lesions on the femur side and 74 multiple lesions according to the part of injury.There was significant difference between the location of osteochondral injury and injury grading(x2=38.153,P<0.05).The ISI,PTI and CDI on the affected side were significantly lower than those on the healthy side in pediatric patients with acute traumatic lateral patellar dislocation of children and adolescents(x2=30.853,12.586,19.656,P<0.05),respectively.Conclusion:The complete tears are more likely to occur in the injury of MPFL patellar attachment location of pediatric patients with acute traumatic lateral patellar dislocation of children and adolescents,while multiple injuries are more likely to be in partial tears.There is correlation between the articular cartilage injury grading and the articular cartilage injury location in pediatric patients.MRI is an important method to diagnose MPFL injury,which can provide more evidence for clinical treatment.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens.GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Background/Aims: Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear. Methods: In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored. Results: Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133 + subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells.Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis. Conclusions Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.

Objective:To study the clinical characteristics and differences between clinical subtypes of neonates with SARS-CoV-2 infection.Methods:From December 11, 2022 to January 10, 2023, neonates with SARS-CoV-2 infection admitted to our hospital were retrospectively studied. The neonates were assigned into two groups according to the clinical classification: the mild group (including asymptomatic, mild and moderate disease) and the severe group (including severe and critical disease). The clinical characteristics were summarized and compared between the groups.Results:Among 162 confirmed cases, 91 (56.2%) were male, 27 (16.7%) were preterm infants and 26 (16.0%) were low birth weight infants (LBWIs). The average age of onset was 15(8,21)d with 125 cases (77.2%) had onset after 7 d of birth. The main clinical manifestations included fever (79.0%), cough (59.3%) and nasal congestion (42.6%). 70 cases (43.2%) had abnormal complete blood count (CBC) with neutropenia most common. 136 cases (84.0%) were in the mild group and 26 in the severe group. The severe group showed higher proportion of male, preterm and LBWIs than the mild group ( P<0.05). The most common clinical manifestation was fever in the mild group and cyanosis in the severe group. Compared with the mild group, the severe group had higher incidence of poor response and longer duration of fever ( P<0.05). No significant difference existed in CBC between the two groups ( P>0.05). 127 neonates received chest X-ray and 77(60.6%) showed pneumonia. 157 neonates were discharged with improvement or full-recovery. The length of hospital stay was 5(3,6)d. 5 patients were discharged refusing further treatment. Conclusions:Most SARS-CoV-2 infections in neonates are mild and moderate types with mild symptoms and fever. A few are severe or critical types with cyanosis the most common symptom. Neonates with poor responses and prolonged fever need to be alerted to the possibility of severe disease, especially for male, preterm and LBWIs. Most neonates have a favorable prognosis.