Objective To investigate the effect of inhibition of glycogen synthase kinase?3 beta ( GSK?3β) activity on sevoflurane postconditioning?induced cardioprotection in diabetic rats. Methods Healthy adult male Sprague?Dawley rats, weighing 250-300 g, in which diabetes mellitus was induced by intraperitoneal 1% streptozotocin 60 mg∕kg combined with high?fat and high?sucrose diet and confirmed by blood glucose level >16. 7 mmol∕L. Forty rats with diabetes mellitus were divided into 5 groups ( n=8 each) using a random number table: sham operation group ( S group ) , ischemia?reperfusion ( I∕R ) group, sevoflurane postconditioning group ( SP group) , GSK?3β inhibitor SB216763 group ( SB group) , and sevoflurane postconditioning plus SB216763 group ( SS group ) . Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfu?
sion. The rats inhaled sevoflurane with the end?tidal concentration of 2.5% for 5 min starting from 1 min be?fore reperfusion in group SP. SB216763 0.2 mg∕kg was injected via the caudal vein at 1 min before reperfu?sion in group SB. In group SS, the rats inhaled sevoflurane with the end?tidal concentration of 2.5% for 5 min starting from 1 min before reperfusion, and SB216763 0.2 mg∕kg was injected via the caudal vein at 1 min before reperfusion. At 120 min of reperfusion, blood samples were collected from the carotid artery for determination of serum creatine kinase?MB (CK?MB) activity and cardiac troponin I (cTnI) concentra?tions. Myocardial specimens were collected at 120 min of reperfusion for microscopic examination of the pathological changes and for determination of myocardial infarct size ( by 2,3,5?triphenyltetrazolium chlo?ride staining) and phosphorylated GSK?3β (p?GSK?3β) expression (by Western blot). Results Com?pared with group S, the myocardial infarct size and serum CK?MB activity and cTnI concentration were sig?nificantly increased, and the expression of p?GSK?3βwas significantly down?regulated in I∕R, SP, SB and SS groups (P<0.05). Compared with group I∕R, the myocardial infarct size and serum CK?MB activity and cTnI concentration were significantly decreased, and the expression of p?GSK?3β was significantly up?regulated in SB and SS groups (P<0.05), and no significant change was found in the parameters men?tioned above in group SP ( P>0.05) . Compared with group SB, the myocardial infarct size and serum CK?MB activity and cTnI concentration were significantly decreased, and the expression of p?GSK?3β was sig?nificantly up?regulated in group SS (P<0.05). The pathological changes of myocardium were significantly attenuated in SB and SS groups as compared with group I∕R and group SP . Conclusion Inhibition of GSK?3β activity can improve sevoflurane postconditioning?induced cardioprotection in diabetic rats.

TNFR-Fc is an important fusion protein that has great potential in therapeutic and diagnostic applications. We developed an efficient fed-batch process for GS-CHO cells to produce TNFR-Fc. The rationale of this fed-batch process relies on the supply of sufficient nutrients to meet the requirements of cell metabolism. The optimal feed medium was designed through ration design. A metabolically responsive feeding strategy was designed and dynamically adjusted based on the residual glucose concentration determined off-line. In this process, the maximal viable cell density and antibody concentration reached above 9.4x10(6) cells/mL and 207 mg/L, respectively. Compared with the batch process, the newly developed fed-batch process increased the cell yield by 3.4 fold and the final antibody concentration by 3 fold. This fed-batch process would therefore facilitate the production of therapeutic antibody by GS-CHO cells.
Animals ; CHO Cells ; Cell Culture Techniques ; methods ; Cricetinae ; Cricetulus ; Culture Media ; Etanercept ; Glucose ; analysis ; Immunoglobulin G ; biosynthesis ; genetics ; Receptors, Tumor Necrosis Factor ; biosynthesis ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics

Objective:To construct a quantitatively diagnostic nomogram model by analyzing the clinical information of patients and the features of multi-modality ultrasound images of thyroid lesions, so as to preoperatively predict the malignant probability of suspicious thyroid nodules and provide effective references for clinical decision-making.Methods:A total of 933 patients, 1 121 thyroid nodules of C-TIRADS 3-5 categories, who underwent surgery in the Second Affiliated Hospital of Harbin Medical University from September 1, 2020 to June 10, 2021 were collected. The nodules were randomly divided into training ( n=897) and test groups ( n=224) in 8∶2 ratio. Finally, the diagnostic performance was evaluated by area under the curve (AUC). Results:①After preliminary screening by univariate analysis, multivariate analysis showed that age, echogenicity, orientation, echogenic foci, margin, posterior features, and elastic score were significantly correlated with benign and malignant nodules (all P<0.001), and the difference of halo between benign and malignant nodules was also statistically significant ( P=0.012). ②The AUC of nomogram was up to 0.903(95% CI=0.862-0.944) in the test set, and 0.889(95% CI=0.832-0.946) and 0.960(95% CI=0.925-0.994) in nodules with maximum diameter of ≤10 mm and of >10 mm respectively, which showed high diagnostic performance. Conclusions:The nomogram model could accurately differentiate malignant from benign thyroid nodules preoperatively, with the highest diagnostic performance for the nodules with maximum diameter of >10 mm, and effectively avoid the unnecessary fine-needle biopsy and surgical operation.

Objective:To investigate the comparative analysis of multimodal ultrasound features and clinicopathology of different molecular types of breast cancer, so as to improve the diagnostic accuracy of different types of breast cancer.Methods:A retrospective analysis of 112 patients with invasive breast cancer in the Second Affiliated Hospital and Affiliated Cancer Hospital of Harbin Medical Univeristy from August 2017 to November 2018 was carried out. With reference to St.Gallen standard, breast masses were divided into four subtypes, including Luminal A (LA), Luminal B (LB), Her-2 overexpression (Her-2+ ) and triple negative (TN). Two-dimensional greyscale, color Doppler flow imaging, shear wave elastography and contrast-enhanced ultrasound images were performed before operation. Complete clinicopathological data were collected. The differences between different subtypes of breast cancer in terms of multimodal ultrasound and clinicopathological features were analyzed.Results:①Luminal breast cancer showed posterior echo attenuation, low Alder grade, low Emax and Eratio value. LA was more likely to show a speculated or angular margin and concentric enhancement; LB was more frequently to show a indistinct margin, low enhancement and no perfusion defect (all P<0.05). ②Her-2+ cancers were characterized with a indistinct margin, enhanced posterior echo, a high Alder grade, Emax and Eratio value, and a high contrast enhancement and perfusion defect. The TTP value was lower than other subtypes (all P<0.05). ③TN cancers were associated with microlobulated margin, posterior echo enhancement, low Alder grade, high Emax and Eratio value and Ki67 expression, contrast concentric enhancement have and perfusion defect (all P<0.05). Conclusions:Different molecular subtypes of breast cancer have different multimodal ultrasound features and clinicopathological appearances, which can provide more imaging information for clinical diagnosis, treatment, and prognosis.

Objective:To compare the efficacy of maxillary distraction osteogenesis (DO) and Le FortⅠ osteotomy (LFⅠ) in patients with complex cleft lip and palate.Methods:A retrospective study was conducted, clinical data were collected involving patients with complex cleft lip and palate who required combined orthodontic and orthognathic treatment and were treated at the Stomatological Hospital of Chongqing Medical University from January 2015 to December 2022. Patients were divided into three groups based on the surgical method used for the maxilla: total maxillary distraction (TMD, group A), anterior maxillary distraction (AMD, group B), and Le Fort Ⅰ osteotomy (LFⅠ, group C). Cone-beam CT scans and lateral cephalograms were obtained preoperatively and at 3 months postoperatively. Three-dimensional reconstructions were performed using Mimics 21.0 and Dolphin Imaging 11.9 software to evaluate changes in craniofacial morphology and airway. Data analysis was conducted using SPSS 25.0. Intragroup comparisons before and after surgery were performed using the Wilcoxon rank sum test, and intergroup comparisons among the three groups were conducted using the Kruskal-Wallis H test. Results:A total of 15 patients were included, with 5 patients in each group. The cohort comprised 8 males and 7 females, aged between 15 and 21 years. There were no statistically significant differences in the distribution of gender, age, or cleft lip and palate classification among the three groups ( P>0.05). Postoperatively, all three groups showed improvement in maxillary hypoplasia. Compared to preoperative measurements, the angle formed by the points A (subspinale), N (nasion), and B (supramentale) (ANB angle) increased in all three groups (all P<0.05). The vertical distance from point A to the nasion perpendicular (A-Nperp) increased in groups A and B ( P<0.05 for both) but not in group C ( P>0.05). The area of the alveolar gap showed an increasing trend in all three groups ( P>0.05). The mandibular plane angle (FMA) decreased postoperatively in group B but showed an increasing trend in the other two groups, though the differences were not statistically significant ( P>0.05). Postoperative airway volume increased or showed an increasing trend in groups A ( P<0.05) and B ( P>0.05) but decreased in group C ( P>0.05). Intergroup comparisons showed significant differences in the angle formed by the sella (S), nasion (N), and point A (SNA angle) and the vertical distance from the anterior nasal spine to the coronal plane (ANS-CP) ( P<0.05). Group A had significantly larger SNA angles and ANS-CP values than group B, and the ANS-CP value in group A was significantly larger than in group C (all P<0.05). There were no other statistically significant differences among the groups ( P>0.05). Conclusion:For patients with severe maxillary hypoplasia due to complex cleft lip and palate, TMD can correct sagittal discrepancies between the upper and lower jaws, increase upper airway volume, but may potentially enlarge the alveolar gap area and increase vertical height of the maxilla. AMD result in less change in maxillary position compared to TMD and is mainly used for patients with severe maxillary dental crowding, needing increased arch length, having minor sagittal discrepancies, or with preexisting velopharyngeal dysfunction. LFⅠ result in changes in maxillary position similar to AMD but less than TMD, making it suitable for patients with moderate maxillary hypoplasia and mild maxillary dental crowding. The advantage of LFⅠ lies in its precise postoperative occlusal design and accurate three-dimensional movement of the jaw.

Objective:To compare the efficacy of maxillary distraction osteogenesis (DO) and Le FortⅠ osteotomy (LFⅠ) in patients with complex cleft lip and palate.Methods:A retrospective study was conducted, clinical data were collected involving patients with complex cleft lip and palate who required combined orthodontic and orthognathic treatment and were treated at the Stomatological Hospital of Chongqing Medical University from January 2015 to December 2022. Patients were divided into three groups based on the surgical method used for the maxilla: total maxillary distraction (TMD, group A), anterior maxillary distraction (AMD, group B), and Le Fort Ⅰ osteotomy (LFⅠ, group C). Cone-beam CT scans and lateral cephalograms were obtained preoperatively and at 3 months postoperatively. Three-dimensional reconstructions were performed using Mimics 21.0 and Dolphin Imaging 11.9 software to evaluate changes in craniofacial morphology and airway. Data analysis was conducted using SPSS 25.0. Intragroup comparisons before and after surgery were performed using the Wilcoxon rank sum test, and intergroup comparisons among the three groups were conducted using the Kruskal-Wallis H test. Results:A total of 15 patients were included, with 5 patients in each group. The cohort comprised 8 males and 7 females, aged between 15 and 21 years. There were no statistically significant differences in the distribution of gender, age, or cleft lip and palate classification among the three groups ( P>0.05). Postoperatively, all three groups showed improvement in maxillary hypoplasia. Compared to preoperative measurements, the angle formed by the points A (subspinale), N (nasion), and B (supramentale) (ANB angle) increased in all three groups (all P<0.05). The vertical distance from point A to the nasion perpendicular (A-Nperp) increased in groups A and B ( P<0.05 for both) but not in group C ( P>0.05). The area of the alveolar gap showed an increasing trend in all three groups ( P>0.05). The mandibular plane angle (FMA) decreased postoperatively in group B but showed an increasing trend in the other two groups, though the differences were not statistically significant ( P>0.05). Postoperative airway volume increased or showed an increasing trend in groups A ( P<0.05) and B ( P>0.05) but decreased in group C ( P>0.05). Intergroup comparisons showed significant differences in the angle formed by the sella (S), nasion (N), and point A (SNA angle) and the vertical distance from the anterior nasal spine to the coronal plane (ANS-CP) ( P<0.05). Group A had significantly larger SNA angles and ANS-CP values than group B, and the ANS-CP value in group A was significantly larger than in group C (all P<0.05). There were no other statistically significant differences among the groups ( P>0.05). Conclusion:For patients with severe maxillary hypoplasia due to complex cleft lip and palate, TMD can correct sagittal discrepancies between the upper and lower jaws, increase upper airway volume, but may potentially enlarge the alveolar gap area and increase vertical height of the maxilla. AMD result in less change in maxillary position compared to TMD and is mainly used for patients with severe maxillary dental crowding, needing increased arch length, having minor sagittal discrepancies, or with preexisting velopharyngeal dysfunction. LFⅠ result in changes in maxillary position similar to AMD but less than TMD, making it suitable for patients with moderate maxillary hypoplasia and mild maxillary dental crowding. The advantage of LFⅠ lies in its precise postoperative occlusal design and accurate three-dimensional movement of the jaw.

Objective:To explore the correlation between tumor markers and prognosis of patients with idiopathic inflammatory myopathy (IIM) associated interstitial lung disease (ILD).Methods:A total of 149 patients who were no less than 18 years old and diagnosed with IIM-ILD from July 2017 to September 2019 in the First Affiliated Hospital of Zhengzhou University were consecutively enrolled in the study. Ten patients were lost to follow-up. The remaining 139 cases were regarded as research objects. Patients were divided into survival group or death group according to their one-year survival status. Then their baseline characteristics were compared. Univariate Cox regression analyses of age, gender, cancer, inflammatory indexes, muscle zymogram, tumor markers, ferritin, melanoma differentiation-associated gene 5 (MDA5) antibody and treatment regimens were conducted to identify prognostic risk factors of one-year mortality. Corrected multivariable cox regression was applied to screen the independent risk factors associated with one-year mortality of IIM-ILD. According to the cut-off value of carcinoembryonic antigen (CEA) and neuron specific enolase (NSE) (6 μg/L and 28 μg/L, respectively), patients were divided into high-level groups and low-level groups. Kaplan Meier survival curve were generated to compare one-year survival rate of high-level groups and low-level groups. On the basis of qualitative results of MDA5 antibody, patients were split into two groups with positive MDA5 antibody or negative MDA5 antibody. The differences of CEA, NSE levels between the two groups and the correlation between CEA, NSE levels and ferritin were analyzed.Results:Age, lactate dehydrogenase (LDH), CEA, carbohydrate antigen (CA) 199, NSE and ferritin in the death group were higher than those in the survival group, while the rate of immunosuppressant administration was lower than that in survival group ( P<0.05). Univariate regression analyses showed that CEA, cytokeratin 19 fragment (CYFRA211) and NSE were risk factors for one-year mortality of IIM-ILD. Adjusted by age, treatment regimens and tumor, multivariate regression analysis showed that CEA [ HR=1.112, 95% CI (1.017-1.214), P=0.019] and NSE [ HR=1.033, 95% CI (1.002-1.064), P=0.034] were independent risk factors for one-year mortality. One-year survival rate of the group with CEA≥6 μg/L was lower than that in the group with CEA<6 μg/L (Logrank test, P<0.001). Similarly, one-year survival rate of the group with NSE≥28 μg/L was lower than that in the group with NSE<28 μg/L (Logrank test, P<0.001). In addition, the CEA level in patients with positive MDA5 antibody was higher than that in patients with negative MDA5 antibody ( P<0.001). However, there was no correlation between NSE and MDA5 antibody. Moreover, serum levels of CEA ( r=0.299, P=0.002) and NSE ( r=0.349, P<0.001) were positively correlated with ferritin. Conclusions:Tumor markers have predictive value for the prognosis of IIM-ILD. Higher CEA and NSE are independent risk factors for poor prognosis in patients with IIM-ILD.

Objective To observe the clinical effect of traditional Chinese medicine bone-setting technique using spinal,pelvi-lower extremity line to treat patients with knee osteoarthritis(KOA).Methods 426 patients with KOA were all from the First Affiliated Hospital of Hebei University of Traditional Chinese Medicine.They were randomly divided into experimental group(384 cases,57 cases of elimination,shedding and termination)by computer generated sequence.Traditional Chinese bone setting techniques were applied with spinal-pelvic-lower limb force line(divided into three parts:lumbar fixed point reduction method,hip joint push-pull and extension method and knee peripheral tendon recovery method every 3 days.2 weeks)treatment;The control group was the waiting treatment group(48 cases,6 cases were eliminated,abscission,termination),which was only used for clinical observation for 2 weeks.The main outcome index was WOMAC pain score.Secondary outcome measures were WOMAC stiffness score,functional score,standardized score and quality of life score(SF-12).The test time points were baseline,2 weeks after enrollment,and follow-up(14 weeks after enrollment).The control group was at baseline and 2 weeks after enrollment.Results Compared with baseline,WOMAC pain score,stiffness score,functional score and standardized score were all decreased in 2 groups 2 weeks after enrollment(P<0.05),but the experimental group was significantly decreased compared with the control group(P<0.001).SF-12 quality of life scores were all higher than before(P<0.001),but the experimental group was significantly higher than the control group(P<0.001).At follow-up,compared with 2 weeks after enrollment,WOMAC pain scores were increased(P<0.001),WOMAC stiffness,joint function and standardized scores were decreased(P<0.001),and SF-12 scores were increased(P<0.001).Conclusion The use of spinal-pelvi-lower extremity line of traditional Chinese medicine bone-setting technique in the treatment of KOA is effective in improving the knee joint function and improving the quality of life of patients,but the short-term effect of pain relief is good,and the long-term effect is not good.Its safety is good,and it can be considered in clinical application for KOA patients with joint dysfunction as the main manifestation.

Objective:To compare the impact of orthodontic treatment on pulp volume in adolescents and adults.Methods:Cone-beam CT data of 62 patients undergoing orthodontic treatment at the Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, from January 2019 to March 2022 were collected. Patients were divided into two age groups (31 patients in each group): adolescent group (aged 13-17, 17 males and 14 females) and adult group (aged 21-25, 12 males and 19 females). Pre-and post-treatment reconstructions of the pulp and dental tissues of upper first molars (UM1) and lower central incisors (L1) were performed. Measurements included pulp volume for UM1 (UM1 P) and L1 (L1 P), pulp chamber volume (UM1 PC) and root canal volume (UM1 RC) for UM1, root length for L1 (L1 RL), and mesiobuccal root length for UM1 (UM1 RL), as well as chamber heights at specific landmarks [the lengths from the central fossa fusion site to the roof of the pulp chamber (H1), the floor of the pulp chamber (H2), the nearest point of root divergence as well as crown-root bifurcation (H3), the farthest point of root divergence (H4), and the pulp chamber height (H5)] in UM1. Changes in these indices were calculated and analyzed using paired and independent sample t-tests for within-group and between-group differences, respectively. Pearson correlation was used to assess potential associations among H5, root length, and pulp volume changes. Results:Before and after orthodontic treatment, no significant difference was observed in the adult group for L1 P ( t=-0.03, P=0.975), while significant differences were noted for UM1 P, UM1 PC, and UM1 RC ( t=9.98, P<0.001; t=9.04, P<0.001; t=6.69, P<0.001). In the adolescent group, significant differences were found for both L1 P and UM1 P ( t=2.25, P=0.029; t=6.30, P<0.001). After orthodontic treatment, the absolute value changes of UM1 P, UM1 PC, and L1 P in the adolescent group were (19.75±9.58), (15.07±7.65) and (1.89±6.29) mm 3, respectively, and in the adult group were (13.33±9.41), (9.16±7.05) and (0.02±4.66) mm 3, respectively ( t=3.77, P<0.001; t=4.48, P<0.001; t=2.34, P=0.048). There was no significant absolute difference in the amount of UM1 RC between the two groups after orthodontic treatment ( t=0.86, P=0.391). Before and after orthodontic treatment, the absolute value changes of L1 RL, H1 and H5 in the adolescent group were (0.54±0.41), (0.38±0.27) and (0.71±0.33) mm, respectively, and the absolute value changes in the adult group were (0.78±0.62), (0.26±0.20) and (0.57±0.28) mm, respectively ( t=-2.43, P=0.017; t=2.96, P=0.004; t=2.57, P=0.011). Whereas no significant differences were observed for UM1 RL, H2, H3, and H4 ( t=-0.85, P=0.400; t=0.43, P=0.669; t=-0.50, P=0.619; t=1.46, P=0.148). Additionally, significant correlations were found between changes in H5 and UM1 RL with UM1 P ( r=0.35, P<0.001; r=0.19, P=0.030), but not between Changes in L1 RL and L1 P ( r=0.11, P>0.05). Conclusions:The effect of orthodontic treatment on pulp volume in adolescents and adults were different.

ObjectiveTo explore the safety and efficacy of robot-assisted minimally invasive esophagectomy （robot-assisted minimally invasive esophagectomy， RAMIE） and thoracic laparoscopy combined with minimally invasive esophageal resection （minimal invasive esophagectomy， MIE）. MethodsThe data of 188 patients treated with Da Vinci robot assisted minimally invasive esophageal resection （RAMIE） from April 2021 to December 2022 were analyzed. In the RAMIE group， 69 patients， 49 males and 20 female， age （67.2 ± 7.2）； 119 in the MIME group， respectively， 89 males and 30 female， age （69.1 ± 7.0）. At 1 ∶ 1， including 58 patients in the RAMIE group and 58 patients in the MIE group. The t-test， Wilcoxon rank-sum test， χ² test， and so on. ResultsAfter PSM treatment， the clinical data between the two groups. There was no significant difference in operation time， postoperative tube days， and total number of lymph node dissection between the RAMIE and MIE groups （P <0.05）； the RAMIE group was better in terms of intraoperative bleeding and the MIE group， statistically significant （P <0.05）； the MIE group was better in drainage flow and lymph node dissection for three days （P <0.05）. In terms of postoperative complications， there was no statistical difference between RAMIE and MIE groups （P>0.05）. ConclusionThe recent efficacy of robot-assisted minimally invasive esophagectomy is comparable to that of thoracic laparoscopy and minimally invasive Mckeown esophagectomy； robotic-assisted minimally invasive esophagectomy can reduce intraoperative bleeding and have more advantages in left recurrent laryngeal nerve lymph node dissection.