OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine （SCOP） and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups： control （0.9% NaCl， n=10）， model （SCOP 1 mg·kg^-1·d^-1， n=10）， low-， medium-， and high-dose Dihuang Yinzi （SCOP 1 mg·kg^-1·d^-1 + Dihuang Yinzi 5.5， 11.0， and 22.0 g·kg^-1·d^-1， n=10）， and donepezil （SCOP 1 mg·kg^-1·d^-1 + donepezil 0.84 mg·kg^-1·d^-1， n=10）. Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week， and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week， 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 （SIRT2）， α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid （AMPA） receptor 1 （GluA1）， protein kinase A （PKA）， cAMP response element-binding protein （CREB）， phosphorylated-CREB （p-CREB）， postsynaptic density protein 95 （PSD95）， growth-associated protein-43 （GAP-43）， and synaptophysin （SYN） in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin （DCX） in the hippocampal dentate gyrus （DG） region. ResultsCompared with the control group， the model group showed impaired learning and memory （P<0.01）， obvious neuronal damage in the hippocampal CA1 region， a reduction in neuron survival （P<0.01）， a decrease in DCX expression in the hippocampal DG region （P<0.01）， down-regulated proteins levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 in the hippocampal tissue （P<0.05， P<0.01）， and an up-regulated protein level of SIRT2 （P<0.01）. Compared with the model group， the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory （P<0.05， P<0.01）， while the low-， medium-， and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival （P<0.05， P<0.01）. The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression （P<0.05， P<0.01）. The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 （P<0.05， P<0.01） and down-regulation in the protein level of SIRT2 （P<0.01）. ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2， activating the PKA/CREB signaling pathway， improving synaptic plasticity， and reducing hippocampal neuronal damage.

Objective To investigate the cause，pathogenesis，clinical manifestations，treatment，and prognosis of secondary hemichorea based on related clinical features and examinations by summarizing the medical records of 25 patients with secondary hemichorea-hemiballism. Methods An analysis was performed for 25 patients with hemichorea-hemiballism who were admitted and treated from July 2018 to April 2024，including general status，clinical features，laboratory examinations，MRI or CT examination，treatment methods，and prognosis. Results Of all 25 patients，11 （44.0%） had acute cerebrovascular diseases [including 7 cases （28.0%） of cerebral infarction，3 cases （12.0%） of cerebral hemorrhage，and 1 case （4.0%） of moyamoya disease]，13 （44.0%） had hyperglycemia，and 1 had unknown causes. Of all 25 patients with hemichorea-hemiballism after treatment of the primary disease and symptomatic treatment，18 patients had significant improvements in hemichorea symptoms，and 7 had disappearance of hemichorea symptoms. One patient experienced recurrence after half a year due to self-withdrawal of medication，and the other patients took medication regularly，with no recurrence at follow-up half a year later.Conclusion Hemichorea-hemiballism is more common in the elderly，and acute cerebrovascular disease is the most common cause of hemichorea-hemiballism，followed by hyperglycemia，with the basal ganglia as the main lesion site. In addition to the treatment of the primary disease，symptomatic treatment with haloperidol，clonazepam，or risperidone can significantly improve clinical symptoms and help to achieve a good prognosis.
Hyperglycemia

Objective:To investigate the clinical features of primary intestinal lymphangiectasia (PIL).Methods:This study was a retrospective case series study. Fifty consecutive patients diagnosed with PIL in Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University from March 2019 to March 2021 were included and their clinical data was retrospectively reviewed. There were 20 males and 30 females included, with an age of ( M(IQR)) 14 (40) years (range:0 to 67 years). No patient had the family history. There were 26 children, including 9 males and 17 females, aged 0 (7) years (range:0 to 14 years). There were 24 adults, including 11 males and 13 females, aged 40 (26) years (range:20 to 67 years). The clinical manifestations and the results of laboratory examinations, gastrointestinal endoscopy, 99Tc m-labeled human albumin ( 99Tc m-HSA) scintigraphy, 99Tc m-DX scintigraphy, direct lymphangiography (DLG), histopathology, diet treatment, surgical intervention, and clinical symptom remission at discharge were collected. Comparisons between groups were performed using independent samples t-test, Mann-Whitney U test, or χ2 test. Results:Among the 50 cases of PIL, the main manifestations were edema (86.0%), diarrhea (76.0%), and abdominal effusion (48.0%). Lymphedema (36.0%) and chylous ascites (18.0%) were not rare in PIL patients. In 99Tc m-HAS scintigraphy, 95.9% (47/49) cases showed signs of intestinal protein loss, and 91.7% (44/48) ceses showed positive findings in 99Tc m-DX scintigraphy. In DLG, 97.8% (45/46) cases showed signs of thoracic duct obstruction, 82.6% (38/46) cases showed retroperitoneal lymphatic hyperplasia, and 23.9% (11/46) cases showed backflow of contrast agent into intestine. No significant difference was seen in gender, course of disease, clinical manifestation, serum level of albumin or globulin, lymphocyte count, positive rate of fecal occult blood and prevalence of lymphedema between adults and children (all P>0.05). Conclusions:The clinical presentations of PIL between children and adults had no significant difference. The diagnosis of PIL should be made according to clinical manifestation, 99Tc m-HAS scintigraphy, 99Tc m-DX scintigraphy, DLG, gastrointestinal endoscopy and pathological findings.

Purpose/Significance The paper discusses the application of artificial intelligence technology to the key entity recognition ofunstructured text data in the electronic medical records of lymphedema patients.Method/Process It expounds the solution of model fine-tuning training under the background of sample scarcity,a total of 594 patients admitted to the department of lymphatic surgery of Beijing Shijitan Hospital,Capital Medical University are selected as the research objects.The prediction layer of the GlobalPointer model is fine-tuned according to 15 key entity categories labeled by clinicians,nested and non-nested key entities are identified with its glob-al pointer.The accuracy of the experimental results and the feasibility of clinical application are analyzed.Result/Conclusion After fine-tuning,the average accuracy rate,recall rate and Macro_F1 ofthe model are 0.795,0.641 and 0.697,respectively,which lay a foundation for accurate mining of lymphedema EMR data.

Objective:To investigate the clinical features of primary intestinal lymphangiectasia (PIL).Methods:This study was a retrospective case series study. Fifty consecutive patients diagnosed with PIL in Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University from March 2019 to March 2021 were included and their clinical data was retrospectively reviewed. There were 20 males and 30 females included, with an age of ( M(IQR)) 14 (40) years (range:0 to 67 years). No patient had the family history. There were 26 children, including 9 males and 17 females, aged 0 (7) years (range:0 to 14 years). There were 24 adults, including 11 males and 13 females, aged 40 (26) years (range:20 to 67 years). The clinical manifestations and the results of laboratory examinations, gastrointestinal endoscopy, 99Tc m-labeled human albumin ( 99Tc m-HSA) scintigraphy, 99Tc m-DX scintigraphy, direct lymphangiography (DLG), histopathology, diet treatment, surgical intervention, and clinical symptom remission at discharge were collected. Comparisons between groups were performed using independent samples t-test, Mann-Whitney U test, or χ2 test. Results:Among the 50 cases of PIL, the main manifestations were edema (86.0%), diarrhea (76.0%), and abdominal effusion (48.0%). Lymphedema (36.0%) and chylous ascites (18.0%) were not rare in PIL patients. In 99Tc m-HAS scintigraphy, 95.9% (47/49) cases showed signs of intestinal protein loss, and 91.7% (44/48) ceses showed positive findings in 99Tc m-DX scintigraphy. In DLG, 97.8% (45/46) cases showed signs of thoracic duct obstruction, 82.6% (38/46) cases showed retroperitoneal lymphatic hyperplasia, and 23.9% (11/46) cases showed backflow of contrast agent into intestine. No significant difference was seen in gender, course of disease, clinical manifestation, serum level of albumin or globulin, lymphocyte count, positive rate of fecal occult blood and prevalence of lymphedema between adults and children (all P>0.05). Conclusions:The clinical presentations of PIL between children and adults had no significant difference. The diagnosis of PIL should be made according to clinical manifestation, 99Tc m-HAS scintigraphy, 99Tc m-DX scintigraphy, DLG, gastrointestinal endoscopy and pathological findings.

Objective To analysis the effectiveness and cost of Internet-based anticoagulation clinic versus traditional anticoagulation clinic treatment at Nanjing Drum Tower Hospital during the COVID-19 pandemic.Methods We reviewed and analyzed the clinical data of patients receiving anticoagulation management through Internet-based outpatient care and traditional outpatient care in Nanjing Drum Tower Hospital,from June 1,2020 to June 30,2021.Variability in time in therapeutic range(TTR)and international normalized ratio(INR)were calculated for enrolled patients.Patients meeting TTR≥60%and INR variability<0.65 were considered optimal anticoagulation quality.Cost-effectiveness analysis was conducted from the patients'perspective,with results expressed using the incremental cost-effectiveness ratio(ICER).Results In the"Internet-based anticoagulation outpatient care"and"traditional face-to-face anticoagulation outpatient care"groups,19 individuals(67.86%)and 67 individuals(76.14%)met the criteria for optimal anticoagulation quality,respectively.The mean TTR was(71.83±19.17)%in the Internet-based group and(71.74±23.41)%in the traditional face-to-face group,indicating similar levels of warfarin anticoagulation quality between the two groups.The ICER was calculated as 327.17 yuan,less than the per capita gross domestic product(GDP)of 2021.Conclusion During the COVID-19 pandemic,Nanjing Drum Tower Hospital's Internet-based anticoagulation outpatient care effectively complemented the government's epidemic control policies.It ensured equivalent anticoagulation outcomes and significantly reduced patients'financial burdens.This approach offers new insights and guidance for optimizing healthcare services in the post-pandemic era.

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.

Objective:To explore the clinical efficacy and safety of single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.Methods:The clinical data of 45 patients who underwent laparoscopic pancreaticoduodenectomy with the procedures of single-layer with full thickness in Second Hospital of Hebei Medical University from Jan 2020 to Jan 2022 were retrospectively collected and compared with 45 matched patients with traditional two-layer pancreaticojejunostomy.Results:The laparoscopic pancreaticoduodenectomy procedures were successfully performed in all the 90 cases. The mean operation time (285.6±92.4 minutes) and the media pancreaticojejunostomy time 20(15, 35) minutes) of the single-layer with full thickness pancreaticojejunostomy group were shorter than those of the two-layer pancreaticojejunostomy group [the mean operation time: 317.0±85.5 minutes, the media pancreaticojejunostomy time: 46(30, 58) minutes] with significantly statistical differences (all P value<0.05). There were no significantly statistical differences on intraoperative blood loss, the postoperative complications or hospital stay between the two groups. Conclusions:Compared with traditional pancreaticojejunostomy, the single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy is simple and safe, which has the advantage of easy manipulation and less time-consuming and can be recommended for laparoscopic procedures.

Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.