ObjectiveTo investigate the effects of Congrong Zonggan capsules （CRZG） on cognitive impairment in the Alzheimer's disease （AD） model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group， low-dose CRZG （0.819 g·kg^-1） and high-dose CRZG （1.638 g·kg^-1） groups， and Donepezilepezil hydrochloride group （2 mg·kg^-1）， with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding， mice were orally administered continuously for six months. On the 5th month of drug administration， Y maze， new object recognition， and Morris water maze tests were conducted separately. After administration， mouse brain tissue was taken， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in brain tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the expression of small glial cell markers Iba1， astrocyte markers GFAP， and amyloid protein 1-42 （Aβ_1-42） in the hippocampus of the brain tissue. The hematoxylin-eosin （HE） staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB （NF-κB） p65， NOD-like receptor protein 3 （NLRP3）， cleaved Caspase-1， apoptosis-associated speck-like protein containing a CARD （ASC）， and other proteins in the brain tissue. ResultsCompared with those in the normal group， the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased， and the discrimination index of novel object recognition was decreased significantly （P<0.01）. The escape latency in the water maze was shortened significantly （P<0.01）. The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ_1-42 in the hippocampus were significantly increased （P<0.01）. There was a significant increase in neuronal lesions， neuronal atrophy， loose arrangement of tissue structure， and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65， cleaved Caspase-1， ASC， IL-6， and IL-1β were significantly increased （P<0.05， P<0.01）. Compared with the model group， the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly （P<0.01）， and the escape latency was shortened significantly （P<0.05， P<0.01）. The content of IL-6 decreased in the brain， and that of TNF-α dropped significantly （P<0.01）. The expression of Iba1 protein and Aβ_1-42 in the hippocampus decreased significantly （P<0.05， P<0.01）. The hippocampal neurons were densely arranged， and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC， cleaved Caspase-1， IL-6， and IL-1β were significantly decreased （P<0.05， P<0.01）. ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease， and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.

Misophonia is a psychophysiological and behavioral disorder characterized by an individual's low tolerance to specific sounds， leading to intense negative emotional experiences and physiological responses. Currently， there is no standardized and universally effective treatment for misophonia in clinical practice worldwide. This article reports the case of an 18-year-old male patient with misophonia who showed poor response to sertraline combined with exposure and response prevention therapy. Subsequently， the patient received 8 weeks of Morita therapy （once a week， 50 minutes per session）， with symptomatic improvement. By presenting this case， we explore the potential efficacy of Morita therapy in treating misophonia， aiming to provide a reference for its clinical management. ［Funded by Scientific Research Development Fund Project of Shandong Second Medical University （number， 2024FYM034）］

Objective:To summarize and analyze clinical characteristics of pediatric mandibular condylar fractures and the long-term therapeutic effects of closed treatment.Methods:A retrospective study was conducted for pediatric condylar fracture in the Department of Oral and Maxillofacial Surgery of Peking University School and Hospital of Stomatology from October 2015 to October 2019, including 33 males (67.3%) and 16 females (32.7%), with an average age of (8.3±2.1) years old. According to the treatment methods, the children were divided into two groups: group A was a removable occlusal splint accompanied with functional exercise, group B was a pure functional exercise. Forty-nine cases (76 sides) children with intracapsular condylar fracture were included in this study. Twenty-three cases in group A and 26 cases in group B. The maximum month opening increased from (20.0±6.2) mm to (46.0±5.3) mm 6 months after closed treatment. Subjective evaluation, special examination, qualitative analysis and quantitative analysis of imaging were used to evaluate the condylar remodeling and functional recovery of temporomandibular joint in two groups of children after closed treatment of intracapsular condyle fracture.Results:There was no significant difference in subjective evaluation, maximum opening examination, mouth open-type, mandibular protrusion, lateral movement and qualitative analysis of imaging at the six-month follow-up after injury. Quantitative imaging measurements showed that the condylar anteroposterior diameter and condylar height in Group B were significantly higher than those in Group A after 1 year of injury.Conclusions:Closed treatment for pediatric condylar fractures can achieve satisfactory results. After 6 months of injury, the children in the two groups could recover the temporomandibular joint function and promote the condylar adaptative remodeling.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

ObjectiveTo investigate the effect of alcohol extract of Oroxylum indicum （MHD-80） on reducing uric acid （UA） and protecting the kidney in the hyperuricemia （HUA） model in vivo. MethodPotassium oxazine （350 mg·kg^-1） and adenine （80 mg·kg^-1） were used to construct an HUA model of mice in vivo to evaluate the mechanism related to UA reduction and the protective effect of renal function of MHD-80. Seventy male ICR mice were randomly divided into seven groups， including the normal group， model group， allopurinol group （5 mg·kg^-1）， febusotan group （5 mg·kg^-1）， and MHD-80 low-， medium-， and high-dose groups （3， 6， 12 mg·kg^-1）， with 10 in each group. Except for the normal group， the other groups were given intragastric administration of potassium oxazine and adenine for 14 consecutive days to establish the HUA model. On the 8^th to 14^th day after modeling， each group was given corresponding drugs by intragastric administration， once a day. 1 h after the last administration， blood was collected from the eyeballs， and kidney and liver tissues of mice were collected. Serum levels of UA， urea nitrogen （BUN）， and creatinine （Cr） and liver activity of xanthine oxidase （XOD） were determined by enzyme colorimetry. Serum contents of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxilin-eosin （HE） staining was used to observe the pathological changes in kidney tissues. The protein expression levels of ATP-binding box transporter G2 （ABCG2） and glucose-facilitating transporter 9 （GLUT9） in kidney tissues were detected by Western blot. ResultIn vivo experiment shows that compared with the normal group， the serum levels of UA， Cr， BUN， inflammatory factors TNF-α， IL-1β， and liver XOD activity in the serum of mice in the model group were significantly increased （P<0.05， P<0.01）， and the expression of GLUT9 in kidney tissues was significantly up-regulated （P<0.05）. ABCG2 protein expression was significantly down-regulated （P<0.05）， and renal injury was obvious. Compared with the model group， the levels of UA， BUN， Cr， TNF-α， IL-1β， and liver XOD activity in the serum of mice in the high-dose group of MHD-80 were decreased to different degrees （P<0.05， P<0.01）， GLUT9 protein expression was significantly down-regulated （P<0.01）， ABCG2 protein expression was significantly up-regulated （P<0.05） in the high-dose group of MHD-80， and the degree of renal injury was reduced. ConclusionMHD-80 has certain uric acid reduction， anti-inflammatory， and anti-renal injury effects， which are related to inhibiting XOD activity and regulating the expression of ABCG2 and GLUT9 uric acid transporter.

Objective:This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) .Methods:A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model.Results:The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions:PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

Objective:To investigate the efficacy of fludarabine and cyclophosphamide combined with rituximab (FCR) in previously untreated patients with chronic lymphocytic leukemia (CLL) .Methods:The clinical data of 43 enrolled patients from May 2004 to December 2017 were analyzed the efficacy and survival results.Results:A total of 43 patients with 31 males and 12 females, and the median age was 58 years old (range 36 to72) before treatment. There were 8 patients with symptom B. The median number of peripheral blood lymphocyte was 26 (3-550) ×10 9/L. IGHV unmutated was detected in 62.1% (18/29) patients, P53 deletion in 14% (6/43) patients, RB1 deletion in 18.6% (8/43) patients, Trisomy 12 in 25.6% (11/33) patients, ATM deletion in 16.7% (7/42) patients, respectively. The median number of treatment courses administered was 4 (range 2-6) . Twenty patients obtained CR (46.5%) , 18 patients obtained PR, 4 patients were SD, 1 patient was PD. The overall response rate (ORR) was 88.37%. Seven patients obtained MRD negative. After the median follow-up time of 51 (6-167) months, median PFS was 67 (29-105) months, median OS was not reach, 5-year PFS was (62.1±8.6) %, 10-year PFS was (31±14.3) %, 5-year OS was (70.5±8.3) %, and 10-year OS was (51.3±13.8) %. Less than 4 courses predicted adverse OS ( P<0.05) . P53 deletion and less than 4 courses were associated with poor PFS ( P<0.001) , and the prognostic value still remained after multivariate analysis[ HR=7.65 (95% CI 1.74-33.60) , P=0.007; HR=3.75 (95% CI 1.19-11.80) , P=0.025]. Eighteen patients (41.9%) appeared grade 2-3 infection after chemotherapy, and 19 patients (44.2%) appeared grade 3-4 hematological adverse reactions. One patient (2.3%) was developed tumor lysis syndrome. All adverse reactions were controlled or recovered spontaneously. Conclusion:Previously untreated CLL patients treated with FCR had a high response rate and good survival rate, which is an important treatment choice for fit patients.

Objective To explore the efficacy and safety of anterior cervical discectomy and fusion assisted with microscope.Methods Thirty-seven patients with cervical spondylosis were included to be retrospectively ana lyzed,including 21 males and 16 females.All these patients had accepted anterior cervical discectomy and fusion (ACDF) assisted with microscope from October,2015 to February,2018,and they were aged from 22 to 77 years old (51.5±6.2 years on the average).In these patients,30 cases were operated on single segment,6 cases were operated on double segments,and 1 case was operated on 3 segments.Among all the patients,15 patients of which (40.54％) had cervical spondylotic myelopathy and 22 patients of which (59.46％) sufferered from cervical spondylotic radicu lopathy.All the operations were performed with a conventional transverse anterior cervical incisions,an intervertebral distractor was placed.The decompression was completed under the microscope,and the fixation was performed under direct vision.Moreover,the operative time,intraoperative blood loss and surgery-related complications were recorded.Follow-up was carried out at different times,including 7 days,1 month,3 months,6 months and every year after operation.Japanese Orthopaedic Association (JOA) score was used to calculate the rate of improvement in neurological function,which can evaluate the clinical efficacy.And cervical dysfunction index (NDI) was used to assess cervical function.Results All patients in this group underwent successful decompression under the microscope.The operation time was 90-160 min,with an average of (110.67±36.42) min;The intraoperative blood loss was 20-110 ml,with an average of (36.00±29.11) ml.All patients were followed-up for 12-31 months,with an average of (15.2±4.7) months.The JOA score improved from 8.37±3.26 preoperatively to 15.96 ± 1.50 at the last follow-up,and its difference had signifi cance in statistics (t=8.592,P=0.000).Neurological function improvement rate could be graded:excellent in 31 cases and good in 6 cases,the excellent and good rate was 100％;NDI was reduced from 19.01 ± 6.47 preoperatively to 5.81 ± 2.58 at the last follow-up,with statistical significant difference (t=5.127,P=0.000).During the follow-up,1 screw was found loosened and slightly withdrawn in 1 female patient at 3 months after operation,of whom had not obvious discomfort.The patient was continuously observed and there was no screw withdrawal again.Moreover,there were no complications such as cerebrospinal fluid leakage,hoarseness and difficulty in swallowing.Conclusion Microscope-assisted ACDF can provide safe and adequate decompression without significantly extending the operation time,which is satisfactory in clinical results.Even in some cases of 1 or 2 segments of intervertebral disc nucleus prolapse,it is possible to avoid a more traumatic ACDF.And it is worthy of clinical promotion.

Objective To present our experience and techniques with the use of autologous costal cartilage grafts in Asian rhinoplasty,and to report the surgical results and complications in 86 consecutive rhinoplasty cases.Methods All operations were performed by the first author (Liu AT) with open approach,costal cartilages and perichondrium were used to reconstruct the nasal tip projection according to the tripod theory in rhinoplasty,after removing the previous injection material,L-shaped implant or hypertrophic scar tissue in the tip.Medical charts and operative records were reviewed retrospectively to summary the complications.Nasal dorsum augmentation was done by costal cartilage or I-shaped allograft,sometimes with anterior sheath of rectus abdominis.Patients' subjective satisfaction of the postoperative nasal appearance was self-evaluated with grading (1 worse,2 no change,3 improved,and 4 much improved).Results From September 2015 to March 2017,86 patients underwent rhinoplasty at our hospital.The postoperative follow-up duration was 6 to 20 months.Overall,functional and aesthetic outcome was satisfactory in most patients,and the mean score by the patients' self-evaluation was 3.3 ± 0.6.Graft exposure,mobility,or significant resorption,pneumothorax or significant donor-site pain were not observed.Conclusions Even with minimal complications and morbidities,autologous costal cartilage grafts in Asian rhinoplasty is a versatile and reliable graft material for nasal tip surgery in severe short or saddle nose,contracted nose due to previous L-shaped augmentation and revision rhinoplasty in which the septal cartilage has already been harvested.

Objective To investigate the tumor molecular mechanism of Hedgehog/Gli in promoting the epithelial-mesenchymal transition (EMT) in gastric cancer AZ521 cells. Methods After 24 h of treatment with GANT61,the mRNA expression of Gli1,Gli2, N-cadherin,and E-cadherin in the AZ521 cell line were detected by real-time fluorescence quantitative PCR. A Western blotting assay was conducted to determine the expression of the above cytokines,p-AKT and AKT. The effect of GANT61 on invasion was observed by transwell assay. N-Shh stimulation of the Hedgehog pathway was conducted to confirm the changes in these cytokines. Results GANT61 significantly downregulated the mRNA expression of Gli1,Gli2,and N-cadherin,but upregulated E-cadherin mRNA expression. The Western blotting assay revealed that GANT61 downregulated the protein expression of Gli1,Gli2,p-AKT,and N-cadherin,but upregulated E-cadherin expression. Furthermore,GANT61 inhibited the invasion. N-Shh proteins up-regulated Gli1,Gli2,and N-cadherin mRNA,protein expression and p-AKT protein expression,but downregulated E-cadherin mRNA and protein expressions. N-Shh promoted the invasion of tumor cells. Conclusion Downregulation of Gli1 and Gli2 can inhibit the invasion and metastasis in gastric cancer cells,which may be related to the promotion of EMT by Gli through the PI3K/AKT pathway.