Objective: To explore the network structure of eating behaviors with anxiety, depression and perceived stress in adolescents, so as to provide a basis for effective prevention and intervention of eating behavior problems and negative emotions in adolescents. Methods: Based on the Psychology and Behavior Investigation of Chinese Residents (2021) database, the study was conducted among 3 087 adolescents. Sakata Eating Behavior Scale Short From(EBS-SF) was used to investigate their eating behaviors. The Patient Health Questionnaire-9(PHQ-9), Generalized Anxiety Disorder Scale-7 Item(GAD-7), and Perceived Stress Questionnaire-3 Item (PSQ-3) were used to evaluate their depression, anxiety and perceived stress. Network analysis method was applied to construct a network of eating behaviors and negative emotional symptoms among adolescents, so as to evaluate the centrality, bridge strength, stability and accuracy of each item. Results: The total scores of eating behaviors, depression,anxiety and stress perception in adolescents were 17.41±4.53,6.95±6.08,4.86±5.03,9.34±3.80,respectively. The symptom with the highest intensity and expected impact was "I am only satisfied when I buy more food than I need", with a node intensity and expected impact value of 4.37. The nodes Depression and Anxiety were the most closely connected(weight=0.87). There were no statistically significant differences in the network structure( M =0.13,0.11) and network connection strength(female and male:4.16,4.06, s =0.10;urban and rural areas:4.08,4.07, s =0.01) between different sexes and residents ( P >0.05). Conclusion The negative impact of comorbidities such as anxiety, depression, perceived stress and eating behaviors among adolescents can be reduced through targeted prevention and intervention of core symptoms and bridging symptoms.

【Objective】 To analyze the genetic variation characteristics and clinical phenotypes of a family with primary microcephaly (MCPH) caused by RTTN gene variation, and to provide reference for genetic counseling and prenatal diagnosis. 【Methods】 Clinical data of the three patients (including 2 fetuses and 2-year-old proband,and one fetus with clinical diagnosis) and their parents were collected and analyzed. Two of the children and their parents were tested by trio whole exome sequencing (trio-WES), sanger sequencing validation sites, and the hazard of their compound heterozygous variants was predicted. Literature review was conducted through domestic and international databases to collect reported RTTN gene mutation cases. 【Results】 Three patients in this family had anomalies of the septum pellucidum, hypoplasia of the corpus callosum and other brain malformations during fetal period. The proband (G2) and fetus (G3) showed intrauterine growth retardation and MCPH in late pregnancy; besides, G2 was born with global developmental delay. Trio-WES detected a c.2101(exon16)C>T(p.Arg701Ter,1526) nonsense and a c.2863(exon22)G>A(p.Glu955Lys)missense in the RTTN gene of G2 and G3, which were inherited from their father and mother, forming a compound heterozygous variant. According to the American College of Medical Genetics and Genomics (ACMG) variant classification guidelines, two variants were likely to be pathogenic (LP) and uncertain significance (VUS). Among them, c.2863(exon22)G>A was a newly discovered missense, which was predicted by the software to be harmful to the gene product. 【Conclusions】 Complex heterozygous variations of RTTN gene (c.2101C>T and c.2863G>A) are the genetic cause of MCPH in this family. This report has enriched the variation spectrum of RTTN gene, provided guidance for prenatal diagnosis and reproduction of this family, as well as material and reference for further understanding of the diseases caused by this gene mutation.

Objective:To prospectively observe the changes of tumor-related symptoms in patients with nasopharyngeal carcinoma following the administration of nimotuzumab one week before radiotherapy.Methods:Non-metastatic nasopharyngeal carcinoma patients with positive epidermal growth factor receptor (EGFR) expression and symptoms caused by the primary lesion or metastatic cervical lymph nodes admitted to Cancer Hospital of Chinese Academy of Medical Sciences were prospectively recruited. Investigators recorded tumor-related symptoms in recruited patients one day before the first administration of nimotuzumab (D0) and conducted follow-up visits from day 2 to day 7 after the first administration (D2-D7) to document symptom changes. All recruited patients were asked to assess tumor-related symptoms on D0 and D7 by visual analogue scale (VAS) scores. VAS scores were analyzed by paired t-test. Results:From June 2020 to April 2023, a total of 21 patients met the inclusion criteria. The median age was 49 years (range: 27-69 years), with a male-to-female ratio of 1.3:1. Among the patients, 17 patients (81%) received concurrent nimotuzumab for 8 cycles, 7 cycles for 3 cases (14%), and 6 cycles for 1 case (5%), respectively. All patients completed symptom assessments as required. The overall response rate of symptoms after the first administration of nimotuzumab was 62%, with response rates of 4/6、5/8、4/10、4/10、4/11、3/11 for tinnitus, headache, aural fullness, secondary pain caused by neck mass, nasal bleeding, and nasal obstruction, respectively. The VAS scores for overall symptoms were significantly decreased after the administration of nimotuzumab one week before radiotherapy ( P<0.001), with the most significant decrease in VAS scores for tinnitus, aural fullness, and headache. Conclusion:The administration of nimotuzumab one week before radiotherapy significantly alleviates tumor-related symptoms in patients with nasopharyngeal carcinoma, particularly in alleviating tinnitus, aural fullness, and headache.

Objective To investigate the clinical efficacy of CT-guided drilling,hematoma aspiration and drainage for senile cerebellar hemorrhage.Methods A retrospective analysis was performed on 89 very old patients(75-89 years old)with cerebellar hemorrhage admitted to our hospital from January 2016 to December 2022.According to their wishes,different surgical treatments were adopted,and thus they were divided into puncture group(42 cases,CT-guided drilling,aspi-ration and drainage for hematoma)and craniotomy group(47 cases,craniotomy).GCS,preopera-tive hematoma volume,length of ICU stay,postoperative complications,mortality rate and the mRS score in 3 months postoperatively in the survival were compared between the 2 groups.Re-sults There were no significant differences in age,male ratio,GCS score,preoperative hematoma volume,recurrence rate at 24 h postoperatively and mortality rate at 3 months postoperatively be-tween 2 groups(P＞0.05).The puncture group had significantly shorter length of ICU stay(7.10±1.43 dvs 8.87±1.39 d,P=0.000)and lower intracranial infection rate(4.76％vs 19.15％,P=0.040)than the craniotomy group.In 3 months of follow-up after surgery,the rate of good mRS score was higher in the puncture group than the craniotomy group,and the mRS score was lower in the former group than the latter one(P＜0.05).Conclusion CT-guided drilling,aspiration and drainage for hematoma can reduce the infection rate and improve the prognosis,and is an effective approach in the treatment of patients over 75 years old with cerebellar hemorrhage.

Objective To assess transcriptomic differences between carbon tetrachloride(CCl4)-induced and diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate(DDC)diet-induced mouse models of liver fibrosis to provide a framework for future research using mouse liver fibrosis models.Methods Mouse models of liver fibrosis were induced by a 10％ CCl4(2 mL/kg)injection or a 0.1％DDC diet.After 4 weeks of induction,serum levels of ALT,AST,and TBil were measured.HE and Sirius red staining were used to observe hepatic inflammation and collagen deposition.Jamall's method was used to evaluate hydroxyproline(Hyp)content in liver tissues.Hepatic tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β were measured by ELISA.Total RNA was extracted from murine liver tissues for RNA-sequencing(RNA-seq).Differentially expressed genes of the two models were analyzed by R software and then GO and KEGG enrichment was performed.Then,genes with significant differences were verified.Results Compared with normal mice,serum levels of ALT,AST,and TBil and hepatic expression of TNF-α,IL-6,and IL-1β were significantly increased in mice that received CCl4 and DDC,while the Alb serum level was decreased.Pathological staining showed that the structures of liver tissues were destroyed and a large number of hepatocytes around the central vein were hyalinized and necrotic in CCl4-treated mice.In DDC diet-treated mice,a large amount of porphyrins had been deposited in the liver and a large number of inflammatory cells had infiltrated into the portal area and bile duct.Different degrees of collagen deposition were observed in the liver tissues of the two model mice.Different genes(DEGs)of CCl4-and DDC diet-treated mice were screened using a filter(|logFC|＞2-fold and P＜0.05).As a result,1820 and 2373 DEGs in CCl4-and DDC diet-treated mice were analyzed,including 1302 and 1978 upregulated genes,and 518 and 395 downregulated genes,respectively.GO annotation showed that the two models had important functions in molecular function,biological process,and cell component.KEGG analysis showed that 22 and 29 signaling pathways were activated in CCl4-and DDC diet-induced models,respectively.Among them,16 signaling pathways,such as extracellular matrix receptor interaction,cell cycle,protein digestion and absorption,focal adhesion,and PI3K-Akt,were significantly enriched in the two models(P＜0.05).Cluster analysis showed that Mup11,Mup15,Mup17,and Mup1 were significantly down-regulated in both models,which were identified by RT-qPCR(P＜0.05).Conclusions This study conducted a comparative analysis of the RNA-Seq transcriptomic features of liver fibrosis models induced by exposure to CCl4 and a DDC diet.It examined the gene expression patterns and the pathways influenced by gene expression.The findings serve as a valuable resource for selecting appropriate animal models for future research on the pathogenesis and treatment of liver fibrosis.

Objective To establish an animal model of dampness-syndrome in mice (single model) and evaluate its characteristics of dampness-syndrome. The above-mentioned mice with dampness syndrome were used to construct mice model of ischemic stroke (double model) and observe the effect of dampness-pathogenic on the outcome of stroke. Methods Healthy C57BL/6J male mice were randomly divided into dampness-syndrome (including sham-surgery group and ischemic stroke group,with 10 mice in each group) and non dampness-syndrome groups (including sham-surgery group and ischemic stroke group,with 10 mice in each group). The dampness-syndrome group was fed with high-fat diet and the non dampness-syndrome group was fed with normal diet for 12 weeks. After the mice model of dampness-syndrome was successfully established,transient middle cerebral artery occlusion/reperfusion (tMCAO/R) surgery was used to replicate an ischemic stroke mice model. Evaluation indicators for dampness-syndrome mice model:the general status including body weight,morphology,posture,activity status,and physical characteristics,the histopathological observation of the aorta (oil red O staining,Masson-trichrome staining) and liver (HE staining,oil red O staining),electron microscopic observation of the tongue tissue (scanning electron microscopy,electron microscopy),blood lipid levels[total cholesterol(TC),triglycerides(TG)]and liver coefficient. Evaluation indicators for ischemic stroke mice model:neurological function score and the cerebral infarction volume ratio. Results Compared with the non dampness-syndrome group,the mice in the dampness-syndrome group showed an increased in body weight,poor hair color,sparse hair,fatigue and laziness,mental atrophy,anorexia and lethargy. It was observed that the aortic lumen was narrowed,the intima was significantly thickened,lipid plaque deposition was increased,and foam cells were visible. A large amount of red lipid droplets appeared in liver cells. There were obvious lipid infiltration and diffuse steatosis. Increased keratosis of the mucosal layer of tongue tissue,the thicker stratum corneum,lipofuscin,and bacteria on the tongue surface were found. Serum TG and TC levels significantly increased(P<0.01),and the liver coefficient significantly decreased (P<0.001). Compared with non dampness-syndrome group (sham-surgery group),neurological function score and the cerebral infarction volume ratio in dampness-syndrome ischemic stroke group obviously increased (P<0.001). Conclusion High-fat feeding for 12 weeks combined with tMCAO/R modeling can successfully establish a mice model with dampness-syndrome ischemic stroke,and the neurological function score and cerebral infarction volume in the dampness-syndrome ischemic stroke group was more severe than that in the non dampness-syndrome ischemic stroke group.

Objective:This study aimed to evaluate the clinical features and treatment outcomes of the value of response-adapted treatment following radiotherapy and induction chemotherapy follwing subsequent comprehensive therapy in patients with resectable locally advanced hypopharyngeal carcinoma. Methods:This cohort study was conducted from September 2010 to September 2020 in our hospital, 231 patients pathologically confirmed stage Ⅲ and ⅣB resectable locally advanced hypopharyngeal carcinoma included. For the IC-directed ART strategy, IC is used to select good candidates to receive radical RT or CCRT, and others undergo surgery. He response-adapted strategy was determined based on the primary tumor response, which was evaluated at a dose of 50 Gy. If the response reached complete response or partial response（more than 80% tumor regression）, patients received radical RT or CCRT; otherwise, they received surgery, if possible, at 4 to 6 weeks after RT. The end points of the study were OS（overall survival）, progression free survival（PFS）, locoregional recurrence-free survival（LRRFS） and LDFS. Results:In IC-directed group, 75.0%（57/76） patients reached PR after 2 cycles of induction chemotherapy. While in RT-directed group, 70.3%（109/155） patients reached large PR at dose of 50 Gy. The median interquartile range follow-up period of the whole cohort was 63.8 months. The 5-year OS, PFS, LRRFS and SFL of the whole cohort were 47.9%、39.6%、44.3% and 36.2%, respectively. In evaluations based on the different treatment strategies, the 5-year OS and SFL were 51.3% versus 37.0%（HR 0.67; 95%CI 0.43-1.05; P=0.07） and 27.8% versus 39.8%（HR 0.68; 95%CI 0.46-0.99; P=0.04） between IC-directed and RT-directed groups. In additional, surgery complications did not significantly differ between these two groups. Conclusion:In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, and higher laryngeal preservation compared with IC-directed strategies. This approach could provide a feasible laryngeal preservation strategy in patients with resectable locally advanced hypopharyngeal carcinoma.
Male ; Humans ; Cohort Studies ; Chemoradiotherapy ; Carcinoma ; Hypopharyngeal Neoplasms/therapy* ; Induction Chemotherapy

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.
Humans ; Carcinoma/diagnosis* ; Oropharyngeal Neoplasms/diagnosis* ; Retrospective Studies ; Neoplasms, Second Primary/diagnosis*

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

ObjectiveTo investigate the therapeutic effect of Yupingfeng San on allergic rhinitis （AR） and its effect on Reactive oxygen species （ROS）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/cysteinyl aspartate specific proteinase-1 （Caspase-1） pathway. MethodSPF mice were randomly divided into control group， model group， loratadine group （0.9 mg·kg^-1）， and low， medium， and high dose Yupingfeng San groups （6， 12， 24 mg·kg^-1）， with 10 mice in each group. The control group was given routine feeding， and the other groups were intraperitoneally injected with ［ovalbumin（OVA） + Al（OH）₃ + phosphate buffer solution（PBS）］ suspension once every other day for seven consecutive times. After seven days， 10% OVA solution was instilled in the nose， two times each day for seven consecutive days. After successful modeling， each administration group was intraperitoneally injected with different doses of Yupingfeng San Decoction， and the control group and model group were intraperitoneally injected with an equal volume of normal saline. Symptoms of sneezing， scratching， and runny nose were recorded and scored daily. The levels of ovalbumin specific immunoglobulin E （OVA-sIgE）， histamine， eosinophil cationic protein （ECP）， prostaglandin D₂ （PGD₂）， interleukin-1β （IL-1β）， interleukin-18 （IL-18）， interleukin-4 （IL-4）， and γ interferon （IFN-γ） in nasal lavage solution and serum of mice were detected by enzyme-linked immunosorbent assay （ELISA）. The damage status of the nasal mucosa was observed by hematoxylin-eosin （HE） staining. The number of goblet cells in the nasal mucosa of mice was observed by periodic acid-Schiff （PAS） staining. The expression of NLRP3 protein in the nasal mucosa of mice was detected by immunohistochemistry. Western blot was used to detect the expressions of NLRP3， cleaved Caspase-1， and cleaved gasdermin D （GSDMD） proteins in the nasal mucosa. The test kit was used to detect the changes in ROS in the nasal cavity of mice in each group. ResultCompared with the control group， the nasal symptoms of the model group were significantly aggravated， and the levels of inflammatory factors OVA-sIgE， histamine， ECP， PGD₂， IL-1β， IL-18， and IL-4 in serum and nasal lavage solution were increased （P<0.05，P<0.01）. The levels of IFN-γ were decreased （P<0.05，P<0.01）. The histopathological score， goblet cell number， and ROS content were significantly increased （P<0.01）， and the expressions of pyrodeath-related proteins NLRP3， cleaved Caspase-1， and cleaved GSDMD were increased （P<0.01）. Compared with the model group， the nasal symptoms of the loratadine group and Yupingfeng San groups were significantly relieved， and the levels of inflammatory factors OVA-sIgE， histamine， ECP， PGD₂， IL-1β， IL-18， and IL-4 in serum and nasal lavage solution were decreased （P<0.05，P<0.01）. The levels of IFN-γ were increased （P<0.05，P<0.01）. The histopathological scores， goblet cell number， and ROS content were significantly decreased （P<0.05，P<0.01）， and the expressions of pyrodeath-related proteins NLRP3， cleaved Caspase-1， and cleaved GSDMD were decreased （P<0.05，P<0.01）. Compared with the loratadine group， the curative effect of the high dose Yupingfeng San group was further increased （P<0.05，P<0.01）. ConclusionYupingfeng San has a therapeutic effect on AR， and its specific effect may be related to the inhibition of ROS/NLRP3/Caspase-1-induced cell pyroptosis.