BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

ObjectiveTo explore the relationship between self-assessed health and age-adjusted Charlson comorbidity index （AICC） in older adults， and to further analyze the differences in this relationship across gender groups. MethodsBased on the China health and retirement longitudinal study （CHARLS） database， this study selected data on basic characteristics， chronic disease status， depressive symptoms， and self-assessed health of older adults aged ≥60 years. Chi-square tests were used to perform a preliminary analysis of the association between these factors and AICC scores. A multifactorial ordered logistic regression model was constructed to assess the effects of each influencing factor on AICC， while multiple linear regression analysis was used to explore the linear relationship between self-rated health and AICC scores. Additionally. Stratified analysis by gender was performed to evaluate gender differences. ResultsA total of 10 911 participants were included， with a mean age of 67.40±5.94 years； 6 249 （57.3%） were male and 4 662（42.7%） were female. The distribution of AICC scores was categorized into low-risk， moderate-risk， higher-risk， and high-risk groups， accounting for 23.5%， 50.2%， 20.6%， and 5.7%， respectively. Multifactorial logistic regression analysis revealed that self-rated health was negatively associated with AICC in the total population and in the male geriatric group （OR=0.843， 95% CI： 0.776， 0.917， P=0.001）， （OR=0.886， 95% CI： 0.796 ， 0.987， P=0.028）， but did not reach statistical significance in the female geriatric group . Linear regression analysis further indicated a significant negative linear relationship between self-rated health and AICC （b=-0.485， 95% CI： -0.516，-0.455， P＜0.001）.This relationship was consistent in both male （b=-0.356， 95% CI： -0.406，-0.305， P＜0.001） and female （b=-0.373， 95% CI： -0.435，-0.310， P＜0.001） subgroups， with a stronger negative association in females. ConclusionSelf-rated health is significantly negatively associated with AICC， and attention should be given to self-rated health in the female geriatric population. Self-rated health can serve as an important tool for identifying elderly group at high risk of comorbidities providing a valuable basis for precise intervention.

Objective To compare endoscopic thyroidectomy via transoral submental approach with open surgery for treating thyroid tumors in terms of the clinical effectiveness.Methods We retrospectively reviewed and analyzed the clinical data and follow-up records of 154 patients in the study,who were hospitalized for thyroidectomy in our hospital from January 2021 to June 2022.Among them,74 cases undergoing endoscopic thyroidectomy via transoral submental approach were assigned to the endoscopic group and 80 cases undergoing traditional open thyroid surgery to the open surgery group.Results All operations were completed successfully and safely in both groups,with no intermediate openings in the endoscopic group.Compared with the open surgery group,the endoscopic group had significantly fewer intraoperative blood losses[(19.46±10.24)mL vs.(32.05±15.87)mL],significantly less incision length[(1.95±0.30)cm vs.(7.05±0.60)cm],significant shorter operative time[(136.66±22.44)min vs.(82.75±15.20)min],and significantly less total postoperative drainage[(111.35±38.92)mL vs.(95.45±36.73)mL](all P＜0.05).Endoscopic patients had superior postoperative pain and cosmetic satisfaction compared to open patients,and the difference was statistically significant(P＜0.05).The two groups had no significant differences in the number of lymph node dissections,parathyroid hormone,and postoperative morbidity between the two groups(P＞0.05).Conclusion The endoscopic thyroidectomy via transoral submental approach can achieve the same clinical effectiveness as the traditional open surgery.However,it is advantageous in reducing intra-operative blood loss,relieving post-operative pain,and achieving a better cosmetic effects of neck incision,thus deserving clinical promotion and application.

Purpose To construct a benign and malignant prediction model of thyroid nodules based on ultrasound image features and clinical features,and to evaluate its diagnostic efficacy.Materials and Methods The data of 121 patients diagnosed with thyroid nodules admitted to the General Hospital of Northern Theater Command from September 2020 to March 2022 were retrospectively analyzed.Taken surgical pathology as the gold standard,there were 70 benign nodules and 51 malignant nodules.Logistic regression was used to analyze the ultrasound image characteristics and clinical data of thyroid nodules,and the characteristic indexes with statistical differences were obtained and a comprehensive prediction model was established.Results There were significant differences in the maximum diameter,morphology,calcification,capsule continuity,blood flow grade,elastography score and contrast-enhanced ultrasound characteristics between benign and malignant thyroid nodules(χ2=11.709,17.707,6.901,12.785,16.984,57.095,98.854,all P<0.05).There were significant differences in age,free thyroxine/free thyroxine ratio,and free thyroxine between the two groups(χ2/t=5.944,2.519,-2.468,all P<0.05).The sensitivity,specificity and accuracy of the clinical model,ultrasonic characteristic model and ultrasonic-clinical combined model were 55.7%,98.6%and 97.0%;72.5%,94.1%and 96.1%;and 61.9%,95.1%and 95.9%,respectively.The area under the curve of the three models were 0.619,0.991 and 0.994,respectively.The diagnostic efficiency of the ultrasonic characteristic model and the combined model was superior to the clinical model,and the difference was statistically significant(Z=-1.75,-2.25,P=0.039,0.012).The area under the curve of the combined model was greater than that of the multi-modal ultrasound model,however,the difference was not statistically significant(Z=-1.60,P=0.054).Conclusion Both the multimodal ultrasound model and the clinical model have certain diagnostic value in predicting benign and malignant thyroid nodules.The diagnostic efficiency of the multimodal ultrasound model is higher than that of the clinical model,and the combined prediction model of the two can improve the diagnostic value.

ObjectiveTo investigate the general situation of defect of vertebral column among primary and middle school students in Minhang District of Shanghai and analyze the related factors， to provide a scientific basis for prevention and treatment. MethodsFrom September to October 2022， a total of 5 715 students were selected from two primary schools， two middle schools， and two high schools in Minhang District for physical examinations and screening for defect of vertebral column. ResultsTotally 219 students had defect of vertebral column， accounting for 3.83% of the sampled population. Anteroposterior spinal abnormalities were found in 4 individuals， accounting for 0.07%， and 218 students had scoliosis， accounting for 3.81%. The detection rate of defect of vertebral column was higher in girls （6.27%） than that in boys （1.51%）， and higher in high school students （10.74%） than in primary school students （1.31%） and middle school students （10.97%）. Students who are mildly underweight （5.95%） and who are moderately to severely underweight （7.46%） had a higher detection rate of defect of vertebral column than those with normal weight （4.54%）， overweight （2.83%）， and obesity （1.60%）. The detection rate among students with poor vision （4.32%） was significantly higher than those with normal vision （2.24%）， with all differences statistically significant （all P<0.05）. ConclusionThe positive rate of defect of vertebral column in primary and middle school students in Minhang District， Shanghai is nearly 4%， with most cases being scoliosis. Factors such as being female， increasing age， being underweight， and poor vision are associated with a higher probability of detecting defect of vertebral column.

Objective:To investigate the clinicopathological features of gonadal neoplastic related lesions in children with disorders of sexual development (DsD).Methods:The clinical manifestations, chromosomal karyotype, histology and immunophenotype of 12 cases of neoplastic related lesions from Guangzhou Women and Children′s Medical Center, Guangzhou were analyzed during Jan 2015 to May 2020.Results:Twelve cases of neoplastic related lesions were screened in 205 cases of DsD, and 6 patients with gonadal germ cell neoplasia aged 3-13 years with an average age of 8.3 years. There were 2 males and 4 females. Clinical features showed malformation of external genitalia in 2 cases, short stature in 2 cases, clitoral enlargement in 1 case, lower abdominal pain and a huge pelvic mass in 1 case. Chromosomal karyotyping of peripheral blood showed 2 cases of 46XY and 4 cases of 45X/46XY. Fourteen gonadal specimens were examined. Microscopically, 1 case showed dysgerminoma in left ovary, and malignant mixed germ cell tumors in right ovary, as well as gonadoblastoma (GB) and undifferentiated gonadal tissue (UGT). The remaining 5 cases were all precursor lesions of germ cell tumor. Six specimens showed GB, 3 of UGT, and 3 specimens showed germ cell neoplasia in situ (GCNIS), one of which was accompanied by intratubular seminoma and 1 was GB with GCNIS. The other 6 patients with DsD were aged from 8 months to 2 years and 5 months, including 5 males and 1 females. Clinical manifestations showed 5 cases of hypospadias and 1 case of bilateral indirect inguinal hernia. Microscopically, 6 cases showed maturation delay of gonocytes in seminiferous tubules. Immunohistochemically, the primordial germ cells/gonocytes expressed OCT3/4, PLAP and c-KIT in the 12 cases.Conclusion:Gonadal neoplasia in children with DsD is mainly precursor lesions of germ cell tumor and improved understanding of these lesions is of great significance.

Objective: To investigate the influences of cardiovascular risk factors on left ventricular wall motion function in patients treated with epirubicin chemotherapy by layer-specific two-dimensional speckle tracking imaging (2D-STI). Methods: Sixty-four female patients with breast cancer treated with epirubicin and 36 controls from June 2018 to March 2019 in Renmin Hospital of Wuhan University were included. According to the numbers of cardiovascular risk factors, the patients were divided into group A (without cardiovascular risk factors, 31 cases), group B (single cardiovascular risk factor, 20 cases), and group C (multiple cardiovascular risk factors, 13 cases). All patients underwent echocardiography before and after epirubicin respectively. Global longitudinal strain, circumferential strain, radial strain (GLS, GCS, GRS), endocardial and epicardial layers of GLS and GCS (endoGLS, epiGLS, endoGCS, epiGCS) were obtained by EchoPAC software analysis. The differences of GLS, EndoGLS, EpiGLS, GCS, EndoGCS, EpiGCS and GRS before and after chemotheraphy were calculated as ΔGLS, ΔEndoGLS, ΔEpiGLS, ΔGCS, ΔEndoGCS, ΔEpiGCS and ΔGRS. Results: Compared with before chemotherapy, GLS, EndoGLS, EpiGLS, GCS, EndoGCS, EpiGCS and GRS were significantly reduced in group A, B and C after chemotherapy (all P<0.05). ΔEndoGLS and ΔEndoGCS showed an increasing trend in groups A, B and C, with statistical significance (all P<0.05). Correlation analysis showed that after chemotherapy with epirubicin, the numbers of cardiovascular risk factors were significantly correlated with strain parameters, and the correlation coefficient of EndoGLS was relatively higher (r=-0.582, P<0.001). Conclusions Layer-specific imaging can reliably detect the influences of cardiovascular risk factors on the left ventricular wall motion function in breast cancer patients treated with epirubicin. Parameters reflecting the endocardial longitudinal systolic function are sensitive indicators for the early detectin of myocardial damage and toxicity by epirubicin in patients with multiple cardiovascular risk factors.

The integrated curriculums of basic medicine in Shanxi Medical University are as follows: nine basic medical courses were integrated into 10 medical modules, with additional training including PBL and TBL case discussion, clinical clerkship, flipped classroom and other non-integrated subjects etc. In order to assess the interest of students for integrated curriculum, their intrinsic motivation, as well as their comprehension and application of medical knowledge, we gave anonymous questionnaire to 149 students, 16 teachers in basic medicine, and 10 teachers in clinical medicine. Results showed that more than 90% students were willing to take the integrated curriculum and participate in PBL and TBL case discussion, and students who were unwilling to take the curriculum were less than 10%, they thought that the knowledge of new curriculum system was incoherent. The proportion of students from higher grade who were unwilling to participate in the flipped classroom was increased from 6.7% to 95.0%. Most of the teachers both in basic and clinic medicine believed that new curriculum system was helpful for students to comprehend basic medical knowledge and strengthen their discriminating ability, but did not function in improving students' practical ability. In the further reform on teaching, details like the coherence of knowledge and the content selected when self-studying should be improved.

Objective: To investigate the pathologic features of gonadal tissues of disorders of sexual development (DSD) in children. Methods: Fifty-three cases of gonadal developmental disorders were collected from July 2015 to August 2017 at Guangzhou Women and Children′s Medical Center. Clinical manifestations, karyotypes, sex hormone levels, ultrasound imaging, histology and immunophenotype of gonadal tissues were analyzed. Results: The age of patients ranged from 7 months to 17 years with an average of (50.7 ± 47.1) months. Social genders of the patients included 32 males and 21 females. Forty-eight patients had abnormal sex hormone levels. Clinical presentations included: toward female genitalia in 25 cases, male genitalia tendency in 17 cases and ambiguous external genitalia in 11 cases. Hypospadias was seen in 31 cases and short stature was seen in 8 cases. Chromosomal karyotyping of peripheral blood revealed 23 cases of sex chromosome disorders, 22 cases of 46 XY disorders, of which 3 cases were 5α-reductase deficiency and 8 cases of 46 XX disorders. Ultrasound examination showed cryptorchidism in 30 cases, including 16 cases of unilateral, 14 cases of bilateral and 1 case presenting a huge pelvic tumor. A total of 97 gonadal tissues from 53 cases of DSD were examined, including 9 cases of unilateral and 44 cases of bilateral gonads. Microscopically, 55 gonads (56.7%) showed dysplastic testes including 17 unilateral and 19 bilateral gonads. Fourteen were streak gonads (14.4%) including 8 unilateral and 3 bilateral gonadal tissues. Nine streak gonad with epithelial cord-like structures (9.3%) were found, of which 5 were unilateral and 2 were bilateral lesions. Seven gonads were ovotestis (7.2%), unilateral in 5 cases (the other side of the gonads of ovary in 4 cases, 1 case of dysplastic testes) and bilateral in 1 case. Seven gonads showed follicular-rich ovarian tissue (7.2%). One case showed bilateral dysplastic testes with gonadoblastoma and ectopic adrenal cortex. One case of streak gonad showed epithelial cord-like structures and undifferentiated glandular tissue embedded in malignant mixed germ cell tumors (mixed gonadoblastoma, dysgerminoma, mature teratoma and yolk sac tumor). One case had testicular microlithiasis. Uterus and fallopian tube structures were found in 11 cases. Immunohistochemical stains were performed in 15 cases. D2-40, PLAP and CKIT were expressed in germ cells and Calretinin, WT1 and inhibin were positive in Setoli cells. SALL4 and OCT3/4 were positive in 3 cases. Inhibin highlighted interstitial Leydig cells in 2 cases. GPC3 was positive in yolk sac tumor component. Conclusions Gonadal dysgenesis presents a broad spectrum of gonadal phenotypes with variable degrees of differentiation. The development of bilateral gonadal tissues has certain variability. Chromosomal karyotypes have no correlation with gonadal phenotypes. Accurate histopathologic diagnosis of gonadal dysgenesis plays an important role in the treatment and prognosis of the patient.

Objective To investigate the effects of different treatment modes on the prognosis of patients with severe trauma.Methods The general data of 396 patients with severe trauma [injurey severity scores (ISS) ≥25] in our hospital emergency for treatment from January 1,2008 to January 1,2012 was collected.The trauma patients were divided into study group and control group.In the study group,the trauma patients were cared by emergency physician of our hospital for pre-hospital treatment during transportation by ambulance since January 1,2010.In the control group,the trauma patients were served with traditional pre-hospital emergency care by the 120 and 999 before January 1,2010.The injury severity score,medical care and outcomes were recorded in trauma database and the efficiency and quality of medical care were compared between two groups.Results The emergency treatment time,length of hospital stays,ICU admission rate,prehospital mortality rate,long-term (6 months) disability rate,and complication rate in the study group were lower than those in the control group,presenting (78.23 ± 21.57) min vs.(96.45 ± 35.14) min,(23.55±12.46) dvs.(28.67±20.72) d,8.1％ (18/222)vs.65.5％ (114/174),13.3％ (34/256) vs.21.6％ (48/222),4.1％ (9/222)vs.9.2％ (16/174),8.1％ (18/222)vs.18.4％ (32/174),in which the differences were statistically significant (P ＜ 0.05).Hospital mortality in the study group was also lower than that in the control group,showing 8.1％ (18/222) vs.12.6％ (22/174),but there was no statistically significant difference (P ＜ 0.05).There was no significant difference in time from occurrence of injury to receiving treatment between the two groups.Conclusion Emergency physicians-cared mode had advantages to improve treatment success rates and reduce mortality in patients with multiple trauma compared with the current conventional emergency mode.It is a good alternative emergency mode.