Evoked Potentials ; Social Isolation ; Attention ; Humans

With a global rise in morbidity rates， obesity has become a pressing public health issue. With increased adipocyte number and volume as the main characteristics， obesity is also manifested by metabolic disorders to varying degrees. At the same time， obesity is a risk factor for diabetes， hypertension， stroke， cancer， and cardiovascular diseases， imposing burdens on society and families. Influenced by lifestyle， environment， behavior， and genetics， obesity is caused by the interaction of many factors， and its pathological process is complex， involving inflammation， autophagy， and intestinal dysbiosis. The mitogen-activated protein kinase （MAPK） cascade reaction， a pivotal signaling pathway， plays a crucial role in cellular processes such as proliferation， differentiation， apoptosis， and stress responses. Both Chinese and international studies indicate that the MAPK signaling pathway can effectively regulate obesity through various pathways， including the modulation of adipocyte differentiation and apoptosis， appetite control， and inflammation improvement. Moreover， traditional Chinese medicine （TCM） has demonstrated significant efficacy in preventing and treating obesity， leveraging advantages such as multiple targets， diverse components， and minimal adverse effects. Research indicates that the MAPK signaling pathway is a primary focus of TCM regulation in this context， although a systematic review in this field is currently lacking. Therefore， this paper， by reviewing the latest Chinese and international research， provided a concise overview of the basic structure of the MAPK pathway， with a specific emphasis on recent progress in TCM interventions targeting the MAPK pathway for obesity treatment. The results indicate that regulating adipose tissue formation， differentiation， and thermogenesis， reducing inflammation and oxidative stress levels， and improving insulin sensitivity and metabolic disorders seem to be the main ways for TCM to regulate the MAPK pathway to prevent and treat obesity. However， it is necessary to find more research methods and explore potential mechanisms underlying TCM formulations based on the MAPK pathway for obesity prevention and treatment.

Objective:To investigate the diagnostic value of a single hydrogen-methane breath test (SHMBT) for small intestinal bacterial overgrowth (SIBO).Method:The current investigation was a cross-sectional study. Questionnaires and SHMBTs were administered to 162 patients with gastrointestinal symptoms (case group) and 69 healthy volunteers (control group). Differences in SHMBT results between the two groups were assessed,and cut-off values of CH 4 (methane) and H 2 (hydrogen) were analyzed via receiver operating characteristic (ROC) curves. Lastly,archived SHMBT data from 2 655 patients with gastrointestinal symptoms (validation set) were used to evaluate the diagnostic value of the SHMBT with respect to SIBO. The Chi-square test,the Mann-Whitney U test,Spearman′s Rank correlation analysis,and the Z test were used for statistical analysis. Results:Based on the international recommended diagnostic criteria for SIBO,which are fasting CH 4 ≥10 ppm (parts per million) or H 2 ≥20 ppm,the SHMBT-positive rate in the case group was significantly higher than that of control group (35.2% vs. 21.7%, χ2=4.08, P=0.043). Levels of CH 4 and H 2 were higher in the case group than in the control group [CH 4: 3(2,7) vs. 3(1,3) ppm, H 2: 11(4,22) vs. 10(5,15) ppm],and the difference in CH 4 levels was statistically significant ( Z=6.22, P=0.001). ROC curves were generated based on whether the subjects had gastrointestinal symptoms. The areas under the ROC curves were 0.633 for CH 4 alone,0.531 for H 2 alone, and 0.620 for CH 4 combined with H 2. The cut-off values were fasting CH 4≥4 ppm,fasting H 2≥13 ppm,and fasting CH 4 ≥5 ppm (or CH 4≥4 ppm and H 2≥24 ppm),respectively. Measuring CH 4 alone and CH 4 combined with H 2 was effective for determining the presence of gastrointestinal symptoms ( P<0.05). When CH 4 alone or CH 4 combined with H 2 were used as diagnostic indicators of SIBO, the respective SHMBT-positive rates in the validation set were 34.2% and 30.4%. These rates did not significantly differ from the SIBO-positive rate of 32.0% obtained via the international recommended diagnostic criteria ( P>0.05). The specificity of CH 4 alone was 79.9%,and the accuracy of CH 4 alone was 68.8%. The specificity of CH 4 combined with H 2 was 85.0%,and the accuracy of CH 4 combined with H 2 was 71.7%. Conclusion:Rapid one-time determination of CH 4 and H 2 in exhaled breath may a viable diagnostic method for SIBO, and using CH 4 combined with H 2 ( i.e.,fasting CH 4≥5 ppm, or CH 4 ≥4 ppm and H 2 ≥24 ppm) as cutoff values may be feasible.

Objective:To identify tooth number abnormalities on pediatric panoramic radiographs based on deep learning.Methods:Eight hundred panoramic radiographs of children aged 4 to 11 years meeting the inclusion and exclusion criteria were selected and randomly assigned by writing programs in Python (version 3.9) to the training set (480 images), verification set (160 images) and internal test set (160 images), taken in Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology between November 2012 to August 2020. And all panoramic radiographs of children aged 4 to 11 years taken in the First Outpatient Department of Peking University School and Hospital of Stomatology from June 2022 to December 2022 were collected as the external test set (907 images). All of the 1 707 images were obtained by operators to determine the outline and to label the tooth position of each deciduous tooth, permanent tooth, permanent tooth germ and additional tooth. The deep learning model with ResNet-50 as the backbone network was trained on the training set, validated on the verification set, tested on the internal test set and external test set. The images of test sets were divided into two categories according to whether there was abnormality of tooth number, to calculate sensitivity, specificity, positive predictive value and negative predictive value, and then divided into four types of extra teeth and missing permanent teeth both existed, extra teeth existed only, missing permanent teeth existed only, and normal teeth number, to calculate Kappa values. Results:The sensitivity, specificity, positive predictive value and negative predictive value were 98.0%, 98.3%, 99.0% and 96.7% in the internal test set, and 97.1%, 98.4%, 91.9% and 99.5% in the external test set respectively, according to whether there was abnormality of tooth number. While images were divided into four types, the Kappa value obtained in the internal test set was 0.886, and that in the external test set was 0.912. Conclusions:In this study, a deep learning-based model for identifying abnormal tooth number of children was developed, which could identify the position of additional teeth and output the position of missing permanent teeth on the basis of identifying normal deciduous and permanent teeth and permanent tooth germs on panoramic radiographs, so as to assist in diagnosing tooth number abnormalities.

Objective:To evaluate the long-term outcomes of posterior release, reduction, fixation, and fusion for irreducible atlantoaxial dislocation (AAD).Methods:Between January 2005 and June 2016, a total of 31 patients with irreducible AAD who had received posterior approach surgery were included. Among them, there were 13 males and 18 females, the average age was 39.1±13.5 years (range 9-72 years). The clinical data of the eligible individuals were collected and analyzed. Neck disability index (NDI) and Japanese Orthopaedic Association (JOA) scores were recorded to evaluate the recovery of neck and neurological functions. The atlantodental interval (ADI), clivus-canal angle (CCA), and cervico-medullary angle (CMA) were measured to evaluate the reduction of AAD. C 0-C 2 angle and C 2-C 7 angle were measured to evaluate the recovery of cervical alignment. For individuals with basilar invagination, the distances from the tip of odontoid process to Chamberlain line and Wackenheim line were measured to assess the reduction in the vertical direction. The duration of bony fusion and complications were also analyzed. Results:The mean follow-up period was 82.7±26.4 months (range 61-170 months). In terms of functional scores, the NDI dropped from 43.41%±11.60% before surgery to 12.19%±6.97% at the six months follow-up, and 9.45%±7.51% at the last follow-up ( F=89.56, P<0.001). The JOA increased from 9.48±2.41 points before surgery to 14.71±1.42 points at the six months follow-up, and 14.97±1.47 points at the last follow-up ( F=52.89, P<0.001). Regarding the horizontal and vertical dislocations, the ADI decreased from 9.16±2.32 mm before surgery to 1.39±1.04 mm at the six months follow-up, and 1.29±1.08 mm at the last follow-up ( F=189.61, P<0.001). The distance from the tip of odontoid process to Chamberlain line decreased from 11.15±4.35 mm before surgery to 2.03±2.83 mm at the six months follow-up, and 2.15±3.02 mm at the last follow-up ( F=37.58, P<0.001). The distance from the tip of odontoid process to Wackenheim line reduced from 6.81±2.57 mm before surgery to -2.23±1.58 mm at the six months follow-up, and -2.27±1.58 mm at the last follow-up ( F=122.16, P<0.001). For the amelioration of the compression on medulla and spinal cord, the CCA increased from 113.68°±12.67° before surgery to 143.39°±7.38° at the six months follow-up, and 142.39°±7.13° at the last follow-up ( F=67.13, P<0.001). The CMA increased from 115.71°±13.69° before operation to 145.58°±10.78° at the last follow-up ( F=41.44, P<0.001). Regarding the curvature of the cervical spine, the C 0-C 2 angle recovered from 1.94°±15.82° before surgery to 14.84°±6.45° at the last follow-up ( F=11.97, P<0.001), and the C 2-C 7 angle ameliorated from 27.26°±8.49° before operation to 19.26°±5.44° at the last follow-up ( F=11.13, P<0.001). Bony fusion was achieved in all cases, the fusion time was 9.71±2.55 months (range 5-15 months). A total of five complications occurred in the cases (two cerebrospinal fluid leakages, one deep infection, one transient neurologic deficit, and one dysphagia). They were all cured with corresponding treatments. In the last follow-up, none of the cases developed failure of internal fixation or re-dislocation. Conclusion:Posterior approach release, reduction, fixation and fusion technique is a safe and efficient surgical strategy with favorable long-term follow-up outcomes for irreducible AAD.

Objective:To investigate the evaluation value of one-stop whole-brain dynamic volume CT angiography and CT perfusion imaging (CTA-CTP) in the cynomolgus monkeys models of middle cerebral artery occlusion (MCAO).Methods:Ten adult cynomolgus monkeys were selected and examined by head and neck CTA-CTP and craniocerebral MRI to rule out craniocerebral space-occupying lesions or cerebrovascular malformation. Under guidance of digital substraction angiography (DSA), the right femoral artery was dissected and monkey autologous thrombosis was injected into the right middle cerebral artery (MCA) through microcatheter to prepare MCAO models. Whole brain DSA was performed intraoperatively to observe whether the model was successfully prepared, and head and neck CTA-CTP was performed 24 h and 7 d after modeling to determine the locations and brain blood flow changes of ischemic lesions. The monkeys were sacrificed 8 d after modeling, and the brain tissues were stained with 2,3,5-triphenyltetrazolium chloride (TTC).Results:Among the 10 cynomolgus monkeys, one was excluded because of preoperative cerebrovascular malformation, and one died of cerebral hernia caused by cerebral hemorrhage during the experiment. The remaining 8 MCAO models were successfully prepared. Intraoperative DSA orthography showed unclear M1 segment and distal branch of MCA. Brain CT scan 24 h and 7 d after modeling showed obvious cerebral ischemic lesions in the right MCA blood supply area, and the infarct extent 7 d after surgery was more obvious than that 24 h after surgery. CTA examination showed obvious blood flow interruption imaging in the in M1 segment of MCA on the right side, the distal vessels were not clearly displayed and the distal branches of the infarct side 7 d after surgery were obvious decreased as compared with those 24 h after surgery. CTP scan showed that the cerebral blood volume of the right cerebrum was obviously reduced as compared with that of the left cerebrum, which was consistent with the blood supply area of MCA; and the infarct cores and penumbra areas 7 d after surgery were obvious increased as compared with those 24 h after surgery. TTC staining showed that the ischemic lesions of the brain tissue on the slices were gray and involved multiple layers, and the range was roughly consistent with the infarction sites shown by DSA and CT imaging.Conclusion:One-stop whole brain dynamic volume CTA-CTP has good evaluation value in imaging findings in MCAO animal models.

Objective:To introduce a new method of root reconstruction for proximal repair of acute type A aortic dissection, and to retrospectively analyze its short-term efficacy.Methods:From January 2018 to October 2019, a total of 455 patients with acute Stanford type A aortic dissection received surgical treatment. Among them, 343 patients underwent double-jacket-wrapping(DJW) root reinforcement(11 patients underwent leaflet suspension), 81 patients underwent Bentall surgery, 15 Wheat operations, 12 untreated roots, and 4 David operations. Compared 343 patients who underwent double-jacket-wrapping root reconstruction and 81 patients who underwent Bentall surgery. The perioperative indicators and short-term survival of the two groups were compared.Results:No patients died intraoperatively. The 30-day mortality rate in the DJW group and the Bentall group were 10.5% and 7.4%, respectively( P=0.403); cardiopulmonary bypass time were(218.8±68.4) min and(240.2 ± 59.8), P=0.011; aortic clamp time were(150.6 ± 47.9) min and(181.3 ±45.6)min, P=0.000. There was no difference between the operation time and the deep hypothermia circulatory time between the two groups. The mean follow-up was(11.7±6.4) months. Seven and two follow-up deaths occurred in the DJW group and the Bentall group, respectively, and the cause of death was not related to the aortic root. The degree of aortic regurgitation after DJW was 0.7±0.5, which was significantly lower than that before surgery( P=0.000). Conclusion:Compared with Bentall surgery, DJW method is a safe and effective method for the repair of acute type A aortic dissection roots, which can obtain good perioperative and early curative effects.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective: To introduce a new method for assessing coronal balance in surgical treatment of scoliosis, and to explore its effectiveness in preventing postoperative coronal imbalance. Methods: The data of forty-six consecutive patients, who underwent posterior surgery for spine deformity correction from January 2016 to December 2016, were retrospectively analyzed. The series included 19 males and 27 females with an average age of 28.24±21.16 years (7-76 years), and with lower instrumented vertebra (LIV) located at the level of L3 or below. Point-line method was used to evaluate coronal balance by determining whether the center of upper instrumented vertebra was located at the measuring rod passing through the centers of symphysis pubis and LIV among all patients during surgery. Preoperative, postoperative 1 week and 3 months Cobb angle, coronal balance distance (CBD), Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), and Scoliosis Research Society Questionnaires-22 (SRS-22) were measured and recorded, and statistical analysis was conducted. And then, subgroup analysis was performed according to preoperative coronal imbalance classification to further evaluate the effectiveness of the new method. Results: Among 46 patients in this study, the prevalence of preoperative coronal imbalance was 47.82% (22/46). Of them, ten patients were type B coronal imbalance and eleven patients were type C coronal imbalance. The prevalence of coronal imbalance at one week after operation was 17.39% (8/46), and the prevalence of coronal imbalance at final follow-up was 10.87% (5/46). The results showed that the mean main Cobb angle was 57.24°±26.51° and 14.71°±10.17° at pre-operation and immediate post-operation, respectively. The difference was statistically significant compared to preoperative value (t=13.211, P=0.000), and the average improvement rate was 73.53%±1.88%. Preoperative coronal balance distance CBD ranged from 2.76 mm to 66.73 mm, with an average of 22.54±13.97 mm; the mean CBD was 16.00±14.85 mm at immediate post-operation. The difference was statistically significant (t=3.665, P=0.001), with an average correction rate of 25.58%±52.39%. Our clinical outcome analysis showed that among 46 patients, the preoperative VAS was 8.11±0.89, and the final follow-up VAS was 4.15±0.79. There was a significant difference between pre-operation and the last follow-up (t=21.529, P=0.000). The preoperative ODI score was 49.76±5.84, and the final follow-up ODI score was 25.74±3.92. The difference was statistically significant (t=44.434, P=0.000). The preoperative SRS-22 was 10.57±2.13, and the final follow-up SRS-22 was 21.89±2.35. Compared to pre-operation, the difference was statistically significant (t=24.023, P=0.000). The subgroup analysis showed that in patients with type B coronal imbalance, the mean Cobb angle correction rate was 70.34%±6.02% at immediate post-operation, and there was a significant difference compared to pre-operation (t=5.437, P=0.000); the average CBD correction rate was 37.45%±29.03%, and significant difference was found (t=2.607, P=0.028). In type C patients, the average Cobb angle and CBD correction rate at immediate post-operation was 72.92%±3.67% and 44.79%±5.63%, respectively, and significant difference was found (t=7.319, P=0.000; t=7.545, P=0.000). Conclusion Point-line method was a simple and effective technique for intraoperative assessment of coronal balance, which could assist surgeons to objectively evaluate the result of restoration of the coronal alignment. The use of point-line method is contributed to improve clinical outcomes of spinal deformity correction surgery, and to prevent the occurrence of postoperative coronal imbalance.

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.