Objective:To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS).Methods:This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute′s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0.Results:From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event.Conclusion:Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.

ObjectiveTo investigate the effect and possible mechanism of prolyl endopeptidase （PREP） on a mouse model of non-alcoholic steatohepatitis （NASH） induced by high-fat diet. MethodsA total of 18 healthy male C57BL/6J mice， aged 6‍ ‍—‍ ‍8 weeks， were randomly divided into normal control group， NASH group， and NASH+rosmarinic acid （RA） group， with 6 mice in each group. The mice in the control group were fed with normal diet for 16 weeks， and those in the NASH group and the NASH+RA group were fed with high-fat diet for 16 weeks； the mice in the NASH+RA group were given the PREP inhibitor RA by gavage since week 9 at a dose of 100 mg/kg， once a day for 8 weeks. The mice were sacrificed after modeling and intervention， and each group of mice was observed in terms of serum inflammatory indicators， the concentration of triglyceride in the liver， and the changes in liver lipids/inflammation/liver fibrosis； NAFLD activity score （NAS） was calculated. Western blot and quantitative real-time PCR were used to measure the protein and mRNA expression levels of PREP， peroxisome proliferator-activated receptor-γ （PPAR-γ）， fibroblast growth factor 21 （FGF21）， and silent information regulator 1 （SIRT1） in liver tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， while the least significant difference t-test and the Dunnett’s-T3 test were used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. ResultsCompared with the NASH group， the NASH+RA group had significant reductions in the serum levels of interleukin-6， tumor necrosis factor-α， and triglyceride （all P<0.05）， as well as significant improvements in hepatic steatosis， hepatocyte edema， inflammatory cell infiltration， and liver tissue lesion. The NASH+RA group had a significant reduction in NAS compared with the NASH group （P<0.05）， and the NASH group had an increase in perivascular collagen fiber with occasional fiber bridging， while the NASH+RA group had a slight reduction in perivascular collagen fiber compared with the NASH group. Compared with the normal control group， the NASH group had a significant increase in collagen area percentage in the liver （P<0.05）， while the NASH+RA group had no significant reduction in collagen area percentage compared with the NASH group. Compared with the NASH group， the NASH+RA group had significant increases in the relative protein expression levels of PPAR-γ， FGF21， and SIRT1 （all P<0.05） and a significant reduction in the relative protein expression level of PREP （P<0.05）. Compared with the NASH group， the NASH+RA group had significant increases in the relative mRNA expression levels of PPAR-γ， FGF21， and SIRT1 （P<0.05） and a significant reduction in the relative mRNA expression level of PREP （P<0.05）. ConclusionPREP reduces the level of inflammation and improves NASH in mice by regulating the PPAR-γ/FGF21/SIRT1 signaling pathway.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

ObjectiveTo explore the effect of Polygonati Odorati Rhizoma polysaccharides on hyperlipidemia in mice by modulating the gut microbiota. MethodsNinety male C57BL/6J mice were randomized into the following groups （n=15）： control， model， simvastatin， low- （100 mg·kg^-1）， medium- （200 mg·kg^-1）， and high-dose （400 mg·kg^-1） Polygonati Odorati Rhizoma polysaccharides groups. Other groups except the control group were fed with a high-fat diet for the modeling of hyperlipidemia， and drug interventions lasted for 12 weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The pathological changes in the liver and epididymal fat were observed by hematoxylin-eosin staining， and lipid accumulation in the liver was assessed by oil red O staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. ResultsCompared with the control group， the model group exhibited an increase in body weight （P<0.01）， along with marked elevations in serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）. Furthermore， the model group showcased increase in the liver index and epididymal fat coefficient （P<0.05）， increased liver fat accumulation， enlargement of adipocytes in the epididymal fat， decreases in both alpha and beta diversity of the gut microbiota， and an increase in the relative abundance of Allobaculum （P<0.01）. Compared with the model group， Polygonati Odorati Rhizoma polysaccharides suppressed the increase in body weight （P<0.01）， lowered the serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）， reduced the liver index and epididymal fat coefficient （P<0.05）， alleviated liver fat accumulation， and decreased the size of adipocytes in the epididymal fat. Furthermore， it enhanced the alpha and beta diversity of the gut microbiota in mice， reduced the relative abundance of Allobaculum， Erysipelotrichaceae， and Clostridium （P<0.01）， and increased the relative abundance of Akkermansia and Blautia （P<0.01）. ConclusionPolygonati Odorati Rhizoma polysaccharides can ameliorate hyperlipidemia induced by a high-fat diet in mice by regulating the diversity and composition of the gut microbiota.

ObjectiveTo explore the effect of a novel initiation model on initiating behavioral requests in children with autism spectrum disorder (ASD). MethodsFrom November to December, 2022, 44 children with ASD were selected from Jiaxing Sunlight Rehabilitation Kindergarten, and divided into prelinguistic group (n = 23) and linguistic group (n = 21) according to the language function. The initiation-requested skills, and types and frequency of initiation-requested behaviors were observed under the novel initiation model and the conventional initiation model. ResultsBoth the groups scored higher in the novel initiation model than in the conventional initiation model for initiation-requested skills (|t| > 2.794, P < 0.05) and types of initiation-requested behaviors (|t| > 3.697, P < 0.01), and it increased for the frequency of the use of two- and three-behavioral initiation of requests (χ² > 7.986, P < 0.05). ConclusionThe novel initiation model can improve initiation request skills in children with ASD.

ObjectiveTo observe the antidepressant effect of Chaihu Shugansan combined with ferulic acid on the rat model of chronic unpredictable mild stress （CUMS） and explore the mechanism from the histomorphology of frontal cortex， expression of key molecules in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrkB） signaling pathway， and changes in monoamine neurotransmitter levels. MethodsSixty adult male SD rats were randomized into six groups （n=10）： blank control， depression model， Chaihu Shugansan （3.3 g·kg^-1·d^-1）， ferulic acid （50 mg·kg^-1·d^-1）， Chaihu Shugansan （3.3 g·kg^-1·d^-1） + ferulic acid （50 mg·kg^-1·d^-1）， and fluoxetine （2.1 mg·kg^-1·d^-1）. Rats in other groups except the blank control group were subjected to a mild chronic unpredictable stress stimulus every day. Seven stimuli were used， including fasting with free access to water for 24 h， water deprivation with free access to food for 24 h， wetting the bedding with water in the cage， restraint for 3 h， tail clamping for 1 min， swimming in ice water at 4 ℃， and day and night reversal. Each stimulus was used 1 to 3 times， and the modeling lasted for a total of 21 days. At the same time of stimulation， rats in each medication group were treated with corresponding agents by gavage， while those in the blank control group and the depression model group received equal volumes of normal saline by gavage. The open field test， sucrose preference test， and forced swimming test were conducted before and after modeling. The rats were anesthetized by intraperitoneal injection of 3% pentobarbital sodium， and the frontal cortex was isolated on ice. The mRNA and protein levels of BDNF， TrkB， and cyclic adenosine monophosphate-responsive element-binding protein （CREB） in the frontal cortex were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of monoamine neurotransmitters 5-hydroxytryptamine （5-HT）， dopamine （DA）， and norepinephrine （NE） in the frontal cortex were determined by enzyme-linked immunosorbent assay. Light microscopy was employed to observe the histopathological changes in the frontal cortex. ResultsCompared with the blank control group， the depression model group showed reduced body mass （P<0.05， P<0.01）， decreased number of crossings and rearings in the open field test and sucrose preference （P<0.01）， prolonged time of immobility in the forced swimming test （P<0.01）， reduced neuronal cells， increased necrotic cells， and darkening cell staining in the frontal cortex， down-regulated mRNA and protein levels of BDNF， TrkB， CREB， and lowered levels of 5-HT， NE， and DA in the frontal cortex （P<0.01）. Compared with the depression model group， each intervention group showed improved general state， increased body mass （P<0.05）， increased number of crossings （P<0.05）， shortened immobility time in the forced swimming test （P<0.01）， increased neuronal cells， reduced necrotic cells， and lightened cellular staining in the frontal cortex， up-regulated mRNA and protein levels of BDNF， TrkB and CREB， and elevated levels of 5-HT， NE， and DA in the frontal cortex （P<0.01）. Moreover， the Chaihu Shugansan + ferulic acid group outperformed the Chaihu Shugansan group and the ferulic acid group in increasing the body mass and the 5-HT content in the frontal cortex （P<0.05）. The combination group outperformed the Chaihu Shugansan group regarding the number of rearings and up-regulation in the mRNA level of BDNF in the frontal cortex （P<0.05）， and it was superior to the ferulic acid group in terms of shortening the immobility time in the forced swimming test， up-regulating the mRNA levels of BDNF， TrkB， and CREB and the protein levels of BDNF and CREB in the frontal cortex， and increasing the DA content in the frontal cortex （P<0.05）. ConclusionChaihu Shugansan combined with ferulic acid can exert antidepressant effect on the rat model of CUMS by regulating the BDNF/TrkB signaling pathway and monoamine neurotransmitter content in the frontal cortex. Moreover， the antidepressant effect of Chaihu Shugansan combined with ferulic acid was more significant than that of Chaihu Shugansan and ferulic acid used alone.

Objective:To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS).Methods:This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute′s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0.Results:From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event.Conclusion:Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.

Objective:To investigate the effects of thoracolumbar vertebral fracture with incomplete spinal cord injury on male sexual function and postoperative prognosis.Methods:A retrospective review was conducted on data from 144 male patients with thoracolumbar vertebral fractures and incomplete spinal cord injuries treated between May 2009 and May 2021 in the Department of Traumatology and Orthopedics at Peking University Third Hospital. Patients ranged in age from 19 to 55 years (mean: 38.6±10.6 years) and underwent posterior incision and reduction internal fixation. The International Index of Erectile Function-5 (IIEF-5), the Premature Ejaculation Diagnostic Tool (PEDT), and the International Spinal Cord Injury Male Sexual Function Basic Data Set were used for sexual function evaluation. Based on the American Spinal Injury Association (ASIA) Spinal Cord Injury classification, changes in neurological and sexual function were assessed at the pre-injury stage, 3 months post-injury, 2 years postoperatively, and at the final follow-up. Factors influencing sexual dysfunction and recovery were analyzed. Spearman correlation analysis was used to identify factors affecting sexual function injury and recovery.Results:A total of 117 patients were included in the final analysis. Follow-up duration ranged from 26.2 to 161.7 months (mean: 74.6±40.5 months). After injury, ASIA grades were distributed as follows: 43 patients with grade B, 41 with grade C, and 33 with grade D. At the 2-year follow-up, 30 patients were grade E, 63 grade D, 19 grade C, and 5 grade B. Improvement in ASIA classification was observed in 90.6% (106/117) of patients: 79 improved by one grade, 27 by two grades, 8 remained unchanged, 1 worsened by one grade, and 2 worsened by two grades. Mean IIEF-5 scores were 19.5±6.4 pre-injury, 8.7±8.0 at 3 months post-injury, and 17.5±7.1 at 2 years postoperatively, with statistically significant differences ( F=123.247, P<0.001). Differences between 3 months post-injury vs. pre-injury and 2 years postoperatively vs. 3 months post-injury were statistically significant ( P<0.05). Mean PEDT scores were 5.3±3.1 pre-injury, 6.9±5.2 at 3 months post-injury, and 6.4±5.1 at 2 years postoperatively, with statistically significant differences ( F=17.014, P<0.001). The difference between 3 months post-injury and pre-injury was statistically significant ( P<0.05), but not between 2 years postoperatively and 3 months post-injury ( P>0.05). At the 2-year follow-up, 96 patients had their IIEF-5 classification restored to pre-injury levels, 85 restored PEDT classifications, and 83 restored both. Post-injury ASIA classification was positively correlated with a decrease in IIEF-5 score and an increase in PEDT score at 3 months post-injury ( P<0.05). Injury segment was positively correlated with the decrease in IIEF-5 score ( P<0.05). Time from injury to surgery showed a positive correlation with increased PEDT score at 3 months ( P<0.05). Post-injury ASIA grade, injury segment, time to surgery, age, intraoperative decompression, and spinal cord function recovery all showed significant correlations with changes in IIEF-5 and (or) PEDT scores at 2 years postoperatively ( P<0.05). According to the International Spinal Cord Injury Male Sexual Function Basic Data Set, the proportion of patients willing to discuss sexual issues increased from 29.9% at 3 months post-injury to 47.9% at 2 years postoperatively ( P<0.05). The proportion of patients with absent or diminished psychogenic erections remained stable (48.7% vs. 48.9%, P>0.05), while those with normal reflexive erections increased from 34.2% to 65.0% ( P<0.05). Conclusion:Thoracolumbar fractures with incomplete spinal cord injury result in reduced erectile function and increased incidence of premature ejaculation. The degree of spinal cord injury and the level of the injured segment are strongly correlated with the extent of sexual dysfunction. At the 2-year postoperative follow-up, 70.9% of patients had recovered sexual function to pre-injury levels.

Objective:To investigate the effects of thoracolumbar vertebral fracture with incomplete spinal cord injury on male sexual function and postoperative prognosis.Methods:A retrospective review was conducted on data from 144 male patients with thoracolumbar vertebral fractures and incomplete spinal cord injuries treated between May 2009 and May 2021 in the Department of Traumatology and Orthopedics at Peking University Third Hospital. Patients ranged in age from 19 to 55 years (mean: 38.6±10.6 years) and underwent posterior incision and reduction internal fixation. The International Index of Erectile Function-5 (IIEF-5), the Premature Ejaculation Diagnostic Tool (PEDT), and the International Spinal Cord Injury Male Sexual Function Basic Data Set were used for sexual function evaluation. Based on the American Spinal Injury Association (ASIA) Spinal Cord Injury classification, changes in neurological and sexual function were assessed at the pre-injury stage, 3 months post-injury, 2 years postoperatively, and at the final follow-up. Factors influencing sexual dysfunction and recovery were analyzed. Spearman correlation analysis was used to identify factors affecting sexual function injury and recovery.Results:A total of 117 patients were included in the final analysis. Follow-up duration ranged from 26.2 to 161.7 months (mean: 74.6±40.5 months). After injury, ASIA grades were distributed as follows: 43 patients with grade B, 41 with grade C, and 33 with grade D. At the 2-year follow-up, 30 patients were grade E, 63 grade D, 19 grade C, and 5 grade B. Improvement in ASIA classification was observed in 90.6% (106/117) of patients: 79 improved by one grade, 27 by two grades, 8 remained unchanged, 1 worsened by one grade, and 2 worsened by two grades. Mean IIEF-5 scores were 19.5±6.4 pre-injury, 8.7±8.0 at 3 months post-injury, and 17.5±7.1 at 2 years postoperatively, with statistically significant differences ( F=123.247, P<0.001). Differences between 3 months post-injury vs. pre-injury and 2 years postoperatively vs. 3 months post-injury were statistically significant ( P<0.05). Mean PEDT scores were 5.3±3.1 pre-injury, 6.9±5.2 at 3 months post-injury, and 6.4±5.1 at 2 years postoperatively, with statistically significant differences ( F=17.014, P<0.001). The difference between 3 months post-injury and pre-injury was statistically significant ( P<0.05), but not between 2 years postoperatively and 3 months post-injury ( P>0.05). At the 2-year follow-up, 96 patients had their IIEF-5 classification restored to pre-injury levels, 85 restored PEDT classifications, and 83 restored both. Post-injury ASIA classification was positively correlated with a decrease in IIEF-5 score and an increase in PEDT score at 3 months post-injury ( P<0.05). Injury segment was positively correlated with the decrease in IIEF-5 score ( P<0.05). Time from injury to surgery showed a positive correlation with increased PEDT score at 3 months ( P<0.05). Post-injury ASIA grade, injury segment, time to surgery, age, intraoperative decompression, and spinal cord function recovery all showed significant correlations with changes in IIEF-5 and (or) PEDT scores at 2 years postoperatively ( P<0.05). According to the International Spinal Cord Injury Male Sexual Function Basic Data Set, the proportion of patients willing to discuss sexual issues increased from 29.9% at 3 months post-injury to 47.9% at 2 years postoperatively ( P<0.05). The proportion of patients with absent or diminished psychogenic erections remained stable (48.7% vs. 48.9%, P>0.05), while those with normal reflexive erections increased from 34.2% to 65.0% ( P<0.05). Conclusion:Thoracolumbar fractures with incomplete spinal cord injury result in reduced erectile function and increased incidence of premature ejaculation. The degree of spinal cord injury and the level of the injured segment are strongly correlated with the extent of sexual dysfunction. At the 2-year postoperative follow-up, 70.9% of patients had recovered sexual function to pre-injury levels.

Objective:To explore the application of contrast-enhanced ultrasound in the preoperative evaluation of carotid body tumor (CBT).Methods:The clinical data of 13 CBT patients undergoing contrast enhanced ultrasound test and surgical treatment at Peking Union Medical College Hospital from Nov 2017 to Aug 2021 was retrospectively analyzed.Results:Among the 13 patients, 7 patients had bilateral lesions. 18 tumors were identified by contrast enhanced ultrasound, which showed rich blood supply, with marked enhancement in 13 tumors and moderate enhancement in 5 tumors. The origins of the arterial supply for tumors were identified by contrast enhanced ultrasound. Time-intensity curve analysis showed that the tumors had enhancement characteristics of fast wash in and slow wash out. The mean contrast wash in time was (3.33±1.40) s, the mean peak intensity was (10.41±1.74) dB, and the mean wash out time was (56.47±22.28) s. A total of 13 cases underwent successful surgical removal. Five cases of external carotid artery ligation and 2 cases of internal carotid artery reconstruction were performed during surgery. Postoperative transient neurological injury occurred in 5 cases. There were no cases of cerebral infarction or death in the perioperative period. Mean postoperative follow-up was 14.31 months. Five cases of neurological injury had satisfactory recovery and no other adverse events occurred.Conclusions:Contrast enhanced ultrasound is an effective method of preoperative imaging assessment for CBT, which helps the surgical planning and preoperative preparation.