Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

BACKGROUND:Currently,there have been studies on three-dimensional digitalization and visualization systems for adult acupoints,but there are not many reports on the visualization of pediatric acupoints based on real pediatric digital sectional anatomical datasets. OBJECTIVE:To design and develop a digital three-dimensional visualization system for children's neck acupoints,to provide a basis for acupuncture and moxibustion,meridian and acupoint science teaching,clinical practice,acupuncture manipulation practice,and acupuncture safety research,and to provide a basis for the development of children's acupoint simulation system. METHODS:Based on a real cross-sectional anatomical dataset of pre-school boys,a three-dimensional digital virtual anatomical model of the neck region of children and internal multi-organ three-dimensional reconstruction were completed using PhotoShop 2021 and Digihuman Reconstruction System software.A database of 11 acupoints was compiled,including Fengfu and Fengchi,using the Unity database language.A three-dimensional model of children's neck anatomy,acupoint database,and writing acupuncture operation codes were integrated in Unity3D software.A three-dimensional digital visualization system for children's neck acupoints was successfully created,which integrated simulation acupoint positioning,three-dimensional acupoint anatomy,acupuncture training,clinical teaching,and acupuncture safety research. RESULTS AND CONCLUSION:(1)This study was based on real child specimens.Manual layer by layer segmentation of cross-sectional images was used to ensure the accuracy of the three-dimensional model to the greatest extent possible.The 3D software Digihuman Reconstruction System was utilized to extract and save independent segmentation data.PhotoShop 2021 software was collaborated with to complete dozens of three-dimensional reconstruction anatomical models of the outer skin of the neck and its internal bone structure,cervical spinal cord,blood vessels and nerves,muscles,and ligaments in children.The basic morphology and overall contour integrity verification of each independent structure were completed in MeshLab software.The 3-material research 13.0 software was applied for final fine tuning and anatomical position confirmation,successfully simulating and restoring the true anatomical morphology of the neck of preschool children.(2)Based on and referring to the national standards of the People's Republic of China,a database of commonly used acupoints in children's neck region was collected and organized,including their names,meridians,positioning,local anatomy,needle insertion levels,acupuncture methods,acupuncture accidents and prevention,acupoint indications,and two-dimensional anatomical sectional images.(3)Unity3D software was employed to integrate the three-dimensional model of children's neck,acupuncture simulation operation,and acupoint database,and a three-dimensional digital children's neck acupoint acupuncture visualization system was successfully constructed.The system displayed information on children's neck acupoints,two-dimensional and three-dimensional anatomical structures,and achieved two-dimensional and three-dimensional acupuncture simulation functions and acupuncture safety research functions for children's neck acupoints.Based on the ultra-thin sectional anatomical dataset of real child specimens,the first three-dimensional digital and visualization system for acupoints in the neck region of children had been constructed.Compared with previous acupoint acupuncture systems,it is more in line with the anatomical and morphological development characteristics of Asian children and has high application value in the fields of acupuncture safety research,clinical teaching,and acupuncture simulation training.

Objective:To explore the effect of Chaibei Zhixian Decoction on intestinal flora and T helper 17/regulatory T cell(Th17/Treg)immune balance in epileptic rats by regulating mammalian target of rapamycin/hypoxia-inducible factor-1α(mTOR/HIF-1α)pathway.Methods:Sixty rats were randomly divided into Sham group,Model group,low-dose Chaibei Zhixian Decoction group(CBZXD-Low)and high-dose Chaibei Zhixian Decoction group(CBZXD-High),with 15 rats in each group.Lateral ventricular injec-tion 1 μl kainic acid(1.5 μg/μl)was used to prepare epileptic rat model,Sham group was injected with an equal amount of physiological saline.CBZXD-Low group and CBZXD-High group were given Chaibei Zhixian Decoction by gavage daily(8.48 g/kg,16.96 g/kg),while Sham group and model group were given an equal amount of physiological saline by gavage.After continuous gavage for 4 weeks,HE staining and Nissl staining were used to detect pathological damage in hippocampal tissue;RT-qPCR was used to detect Th17/Treg related marker mRNA levels in spleen tissue and mTOR,HIF-1α mRNA levels in hippocampus tissue;flow cytometry was used to de-tect Th17/Treg cell ratio in spleen tissue;16S rRNA sequencing of feces in colon segment was performed;Western blot was used to de-tect mTOR and HIF-1α protein levels in hippocampal tissue.Results:Compared with Sham group,Model group rats suffered from spontaneous epilepsy,the arrangement of hippocampal neurons was disordered and severely lacking,intracellular Nissl bodies was de-creased,RORγt,IL-17A mRNA levels in spleen tissue were increased,Foxp3,CTLA-4 and GITR mRNA levels were decreased,the proportion of Th17 cells and Th17/Treg were increased,the proportion of Treg cell was decreased,intestinal flora α/β diversity were decreased,the proportion of harmful bacteria such as Cronobacter and Heliobacillus were increased,the proportion of beneficial bacte-ria such as Bacteroides,Lactobacillus,Prevotella and Akkermansia were decreased;mTOR and HIF-1α mRNA levels,p-mTOR/mTOR,HIF-1α protein levelsin hippocampal tissue were increased(P<0.05);compared with Model group,the seizures of rats in CBZXD-Low group and CBZXD-High group were significantly reduced,and the damage to hippocampal neurons was alleviated,RORγt,IL-17A mRNA levels in spleen tissue were decreased,Foxp3,CTLA-4 and GITR mRNA levels were increased,the propor-tion of Th17 cells and Th17/Treg were decreased,the proportion of Treg cell was increased,intestinal flora α/β diversity were in-creased,the proportion of harmful bacteria such as Cronobacter and Heliobacillus were decreased,the proportion of beneficial bacte-ria,such as Bacteroides,Lactobacillus,Prevotella,and Akkermansia were increased;mTOR and HIF-1α mRNA levels,p-mTOR/mTOR,HIF-1α protein levels in hippocampal tissue were decreased(P<0.05);and it showed a dose-dependent effect of Chaibei Zhixian Decoction(P<0.05).Conclusion:Chaibei Zhixian Decoction can restore intestinal flora and Th17/Treg cell immune balance in epileptic rats,it possibly plays a role by regulating mTOR/HIF-1α pathway.

The advancement of surgical techniques enables effective treatment for many patients with oral and maxillofacial tumors.How-ever,post-surgery problems such as chewing,swallowing and speech difficulty may arise due to the defects in speech organs and inade-quate compensatory function of tissue flap repair.Speech disorders,in particular,isolate patients by making it difficult for them to com-municate with others,not only impact their quality of life but also potentially lead to psychological problems and social interaction disor-ders.Although the decline in life quality and other related issues caused by speech dysfunction due to surgery and radiotherapy or chemo-therapy have been widely recognized,there is currently no standardized and universally applicable assessment method and standardized re-habilitation treatment management guideline or consensus for speech disorders following oral and maxillofacial tumor surgery at home and abroad.Based on previous clinical practice,combined with the characteristics of speech disorders in patients after oral and maxillofacial tumor surgery,the clinical experience of the experts in maxillofacial tumor surgery and rehabilitation and the relevant domestic and foreign literature,relevant experts organized discussions and modifications,reach a consensus on core content such as the assessment of speech disorders and the implementation plan for early rehabilitation treatment management,providing a reference for clinical practice,in order to improve patients'speech-related life quality and enhance the assessment and rehabilitation treatment techniques for speech disorders after oral and maxillofacial tumor surgery.

OBJECTIVE: To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS). METHODS: A adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X). RESULTS: Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c.206+2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the proband's mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION The heterozygous splice site variant c.206+2T>G of the SMAD3 gene probably underlay the disease in this patient. Above discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.
Adult ; Humans ; Male ; Exome Sequencing ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Pedigree ; Smad3 Protein/genetics*

Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

Objective:To investigate the characteristic distribution of vaginal microbiota in infertile women.Methods:We collected the results of vaginal microbiological examinations from 19322 initial visit infertile women who visited the Reproductive Medicine Center of the Department of Obstetrics and Gynecology,the Second Affili-ated Hospital of Air Force Medical University from March 1,2023 to July 31,2024.The vaginal microbiota infection status of patients was compared in different age groups(＜25 years old,25-＜30 years old,30-＜35 years old,35-＜40 years old,≥40 years old)and different seasons(spring,summer,autumn,winter).Results:①Among 19322 women,6027 cases(31.19％)showed abnormal vaginal microecology.Pathogenic microorganisms were detected in 3093 cases,including 2882 cases of single vaginitis,211 cases of mixed vaginitis,3764 cases with vagi-nal cleanliness grade Ⅲ-Ⅳ,and 3965 cases with abnormal lactobacilli.Among patients with single vaginitis,1349 cases(46.81％)were diagnosed with vulvovaginal candidiasis(VVC),which was the highest proportion.Aerobic vaginitis(AV)followed with 752 cases(26.09％),and bacterial vaginosis(BV)had 671 cases(23.28％),trichomonal vaginitis(TV)with 110 cases(3.82％).Among patients with mixed vaginitis,AV+BV was the most common with 96 cases(45.49％).②The detection rates of cleanliness grade Ⅲ-Ⅳ,abnormal lactobacilli,abnor-mal microorganisms(unclear pathogen),single vaginitis(BV,VVC and TV),and mixed vaginitis showed statisti-cally significant differences across different seasons(P＜0.05).Specifically,the detection rates of cleanliness grade Ⅲ-Ⅳ and abnormal microorganisms(unclear pathogens)were significantly higher in autumn than in other seasons(P＜0.05),while the detection rate of abnormal lactobacilli was higher in spring than in other seasons(P＜0.05).③The detection rates of abnormal lactobacilli,abnormal microorganisms(unclear pathogen),single vaginitis(BV,VVC and AV),and mixed vaginitis showed significant differences among different age groups(P＜0.05).Specifically,the detection rate of abnormal microorganisms(unclear pathogen)was higher in the age group＜25 years than in other age groups(P＜0.05),while the detection rate of BV among single vaginitis cases was higher in the age group≥40 years than in other age groups(P＜0.05).Conclusions:The vaginal microecol-ogy of infertile women varies in terms of infection rates across different age groups and seasons.Patients with simple vaginitis have the highest rate of VVC,while those with mixed vaginitis have the highest proportion of AV+BV infection.

Objective To investigate the clinical features,treatment and prognosis of primary testicular lymphoma(PTL),so as to provide reference for the standardized diagnosis and treatment of this disease.Methods Clinical data of 13 PTL cases treated in Xijing Hospital during Jan.2014 and Dec.2024 were retrospectively collected.The patients' diagnosis,treatment methods and prognosis were summarized.Results All 13 patients underwent orchiectomy of the affected side.According to the postoperative pathological results,11 cases were diagnosed as diffuse large B-cell lymphoma and 2 as NK/T-cell lymphoma.Among the 11 cases with diffuse large B-cell lymphoma,10 received immunotherapy and chemotherapy according to the international standardized treatment plan,and 5 received preventive myeloablative injection therapy.Recurrence in the contralateral testis occurred in 3 cases,1 complicated with central nervous system infiltration died,and another 1 refusing chemotherapy had contralateral testicular metastasis.Of the 2 cases with NK/T-cell lymphoma,1 received systemic chemotherapy and died after central nervous system recurrence,and another 1 died 1 month after surgery whithout undergoing chemotherapy.Conclusion Primary testicular lymphoma is highly invasive with poor prognosis.Patients with NK/T-cell lymphoma have extremely poor prognosis,while those with diffuse large B-cell lymphoma have relatively better prognosis.However,even after comprehensive treatment,it is still prone to recurrence in the testis and the central nervous system.

BACKGROUND:With the increasing attention of scholars at home and abroad to children's cervical spine-related diseases,the demand for exploring the anatomical indicators and changes of cervical spine morphology and development in children of different ages is increasing.OBJECTIVE:To explore and analyze the morphological changes of children with different ages and vertebral sequences by measuring the anatomical position indexes of C2-C7 neurocentral synchondrosis in children aged 1-6 years.METHODS:Normal cervical spine CT images were retrospectively collected from 160 children aged 1-6 years at provincial tertiary hospitals.They were divided into six groups according to an age group of 1 year.The raw data of consecutively scanned cervical spine tomography images were imported into Mimics 16.0 software.The positional anatomical indexes of cervical spine segments C2-C7 in coronal and transverse planes were measured and analyzed under the two-dimensional image window by choosing the measurement tools under the toolbar of Measurements.RESULTS AND CONCLUSION:(1)The distance between the two sides of C2-C7 neurocentral synchondrosis and the distance between the left and right sides of neurocentral synchondrosis and the transverse process gradually increased with age.The overall development of vertebrae in each cervical vertebral segment was faster than the ossification of the neurocentral synchondrosis.(2)The cross-sectional angles on both sides of C2-C7 neurocentral synchondrosis gradually increased with age,and the angles between the left and right sides of neurocentral synchondrosis and the anterior and posterior edges of the vertebral body gradually decreased.Both sides of the neurocentral synchondrosis in cervical vertebral segments tended to grow toward the arch site,which mainly promoted the growth and development of the arch.(3)Except for C7,the angle between the coronal planes on both sides of the cervical spine changed little with the descending neurocentral synchondrosis of the cervical spine,and the neurocentral synchondrosis of the cervical spine was more inclined to longitudinal growth and ossification.(4)The neurocentral synchondrosis position changes in C7 were significantly different from those in the rest of the cervical vertebrae.(5)The anatomical indexes of C2-C7 neurocentral synchondrosis position in children have obvious development rules among different ages and vertebral bodies,and these rules are helpful for the clinical diagnosis and treatment of cervical spine diseases in children.

Objective:To explore the impacts of carnosic acid(CA)on learning and cognitive function in epileptic rats and the mechanism of regulating PKA-CREB signaling pathway in this process.Methods:Epilepsy rat models were prepared by intraperi-toneal injection of 50 mg/kg PTZ.After successful modeling,the rats were randomly grouped into control group,model group,CA low-dose group,CA high-dose group,CA high+PKA inhibitor group(CA high+H-89 group),with 15 rats in each group.The epileptic be-havior of rats in each group was evaluated;Morris water maze experiment was applied to test the cognitive ability of rats;HE staining and Nissl staining were applied to detect the morphology of hippocampal tissue and neurons of rats in each group;ELISA was applied to detect the contents of IL-1β,TNF-α,MDA,and the SOD activity in the hippocampus of rats in each group;and Western blot was applied to detect the protein expressions of PKA,p-PKA,CREB,p-CREB and BDNF in the hippocampus of rats in each group.Results:Compared with control group,the hippocampal neurons of rats in model group were irregularly arranged,with pyknosis of the nuclei,and the number of neurons decreased,the epilepsy frequency,Racine grading,escape latency,time of first platform crossing,and levels of IL-1β,TNF-α and MDA all increased,the frequency of crossing the platform,SOD activity,p-PKA/PKA,p-CREB/CREB,and the expression of BDNF protein all reduced(P<0.05);compared with model group,the arrangement of neuronal cells in hippocampal tissue of rats in CA group gradually became orderly,nuclear pyknosis gradually decreased,and the number of neurons increased,the epilepsy frequency,Racine grading,escape latency,time of first platform crossing,and levels of IL-1β,TNF-α and MDA all reduced,the frequency of crossing the platform,SOD activity,p-PKA/PKA,p-CREB/CREB,and the expression of BDNF protein all increased(P<0.05);further injection of PKA inhibitors on the basis of high-dose CA treatment showed that the improvement effects of high-dose CA on cognitive dysfunction,neuronal damage,inflammation,and oxidative stress in epileptic rats were reversed(P<0.05).Conclusion:CA can improve the learning and cognitive function of epileptic rats by activating the PKA-CREB signaling pathway.