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

Objective Jejunal interposition is an important option for restoring gastrointestinal continuity in patients with complex esophageal cancer in whom the stomach is unavailable for reconstruction due to previous gastrectomy, tumor involvement, failed gastric conduit, or other constraints. Although the jejunum offers a caliber similar to the esophagus, a rich blood supply, and preserved peristaltic function, anatomical variations in mesenteric length and vascular arcades render long-segment and high-level reconstruction susceptible to excessive tension, mesenteric torsion, venous congestion, and inadequate distal perfusion. This consensus aims to provide standardized recommendations for the application of jejunal interposition in this specific patient population. Methods This consensus was developed in accordance with the WHO Handbook for Guideline Development and Chinese national guideline development standards, with reference to the Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ), Reporting Items for Practice Guidelines in Healthcare (RIGHT), and Scientific, Transparent and Applicable Rankings (STAR) checklists. The project was registered on the international practice guidelines registry platform (PREPARE-2026CN1384). The working group systematically searched Chinese and English evidence addressing 12 clinical questions. Evidence was graded using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 system, with structured appraisal of risk of bias, inconsistency, indirectness, and imprecision. Recommendations were formulated through two rounds of Delphi surveys and a face-to-face consensus meeting, with an agreement threshold of ≥75%. Results The consensus generated 12 recommendations covering indications, selection between jejunum and colon, preoperative assessment, surgical approach and reconstruction route, pedicled jejunal interposition (PJI), supercharged pedicled jejunal interposition (SPJ), indocyanine green (ICG) perfusion assessment, perioperative nutrition, management of anastomotic leakage, long-term follow-up, and special treatment scenarios. Given that the available direct evidence is predominantly derived from single-center retrospective cohorts and case series, recommendations extrapolated from general esophagectomy or other gastrointestinal surgical evidence are deliberately phrased with caution. Conclusion Jejunal interposition is a safe and effective approach for digestive tract reconstruction in patients with complex esophageal cancer in whom the stomach is unavailable. This consensus emphasizes that clinical decision-making should be individualized based on the patient's prior treatment history, reconstruction height, vascular anatomy, technical availability, and institutional experience in the Chinese context.

Objective To explore the therapeutic effect and influencing factors of individualized exercise under continuous glucose profile in patients with typ 2 diabetes mellitus(T2DM).Methods A total of 110 patients with T2DM who were treated in the Department of Endocrinology of our hospital from December 2021 to July 2022 were randomly divided into conventional group and personalized group,with 55 cases in each group.The conventional group was given routine health exercise guidance,the personalized group was given a personalized exercise program.Repeated measurement analysis of variance was used to evaluate the improvement of blood glucose related indicators in the two groups at 3 and 6 months after intervention.Logistic regression was used to analyze the influencing factors of blood glucose(BG)control after 6 months of intervention.Results After 3 and 6 months of intervention,FBG,2 hBG,hemoglobin A1c(HbA1c),mean blood glucose(MBG)and time above target range(TAR)in the personalized group and conventional group were all lower than those before intervention(P<0.05).Time in range(TIR)of glucose within 24 h was higher than that before intervention(P<0.05).After 3 and 6 months of intervention,FBG,2 hBG,HbA1c,MBG and TAR in the personalized group were lower than those in the conventional group at the same time point(P<0.05),and TIR was higher than that in the conventional group at the same time point(P<0.05).After 6 months of intervention,the BG control rate in the personalized group was higher than that in the conventional group(P<0.05).Logistic regression analysis showed that the DM duration,exercise intervention methods and TIR were the influencing factors of BG control.Conclusions Exercise guidance is an effective intervention method to control diabetes.Compared with conventional exercise guidance,personalized exercise program has a better effect on controlling patients'BG level,and has a better effect on patients with short course of disease.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

OBJECTIVES: To evaluate the value of ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT imaging in staging and treatment decision for gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). METHODS: This retrospective analysis was conducted in 49 patients with GEP-NEN undergoing ¹⁸F-FDG and ⁶⁸Ga-DOTATATE PET/CT imaging at our hospital from August, 2020 to March, 2023, including 34 newly diagnosed patients and 15 patients with recurrence or metastasis after treatment. GEP-NEN were classified into G1, G2, and G3 neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC) based on pathological typing. The detection efficiency were classified into 4 patterns based on the number of positive tumor lesions detected by the two tracers: ⁶⁸Ga-DOTATATE>¹⁸F-FDG (A); ⁶⁸Ga-DOTATATE=¹⁸F-FDG (B); ⁶⁸Ga-DOTATATE<¹⁸F-FDG (C); and complementation (D). The value of dual-modality imaging in staging and treatment decision were evaluated by visual analysis. RESULTS: In the 49 patients with GEP-NEN, ⁶⁸Ga-DOTATATE PET/CT was superior to ¹⁸F-FDG PET/CT for detecting systemic tumor lesions (P<0.001) and more sensitive for detecting primary/recurrent lesions, lymph node metastasis, liver metastasis, and bone metastasis (P<0.05), while ¹⁸F-FDG PET/CT had higher detection rates for lung metastasis and peritoneal metastasis (P<0.05). In terms of the detection efficiency, Pattern A was found in 46.9% (23/49) patients, Pattern B in 38.8% (19/49), Pattern C in 12.2% (6/49), and Pattern D in 2.0% (1/49). The complementary value of ¹⁸F-FDG PET/CT to ⁶⁸Ga-DOTATATE PET/CT was 0% in G1 NET patients (0/13), 8.3% in G2 NET patients (2/24), 50% in G3 NET patients (3/6), and 33.3% in NEC patients (2/6). 12.2% (6/49) of the patients had their staging confirmed or changed due to additional lesions detected by ¹⁸F-FDG PET/CT imaging, resulting subsequently in establishment or adjustment of their treatment plans. CONCLUSIONS ⁶⁸Ga-DOTATATE PET/CT imaging should be the primary choice for GEP-NEN patients. Additional ¹⁸F-FDG PET/CT imaging can potentially improve precision of staging and treatment decision-making for G2, G3 and NEC patients but provides virtually no clinical benefits for G1 NET patients.
Humans ; Positron Emission Tomography Computed Tomography/methods* ; Neuroendocrine Tumors/therapy* ; Pancreatic Neoplasms/therapy* ; Retrospective Studies ; Organometallic Compounds ; Stomach Neoplasms/therapy* ; Neoplasm Staging ; Fluorodeoxyglucose F18 ; Intestinal Neoplasms/therapy* ; Female ; Male ; Middle Aged ; Aged ; Adult

Objective To explore the therapeutic effect and influencing factors of individualized exercise under continuous glucose profile in patients with typ 2 diabetes mellitus(T2DM).Methods A total of 110 patients with T2DM who were treated in the Department of Endocrinology of our hospital from December 2021 to July 2022 were randomly divided into conventional group and personalized group,with 55 cases in each group.The conventional group was given routine health exercise guidance,the personalized group was given a personalized exercise program.Repeated measurement analysis of variance was used to evaluate the improvement of blood glucose related indicators in the two groups at 3 and 6 months after intervention.Logistic regression was used to analyze the influencing factors of blood glucose(BG)control after 6 months of intervention.Results After 3 and 6 months of intervention,FBG,2 hBG,hemoglobin A1c(HbA1c),mean blood glucose(MBG)and time above target range(TAR)in the personalized group and conventional group were all lower than those before intervention(P<0.05).Time in range(TIR)of glucose within 24 h was higher than that before intervention(P<0.05).After 3 and 6 months of intervention,FBG,2 hBG,HbA1c,MBG and TAR in the personalized group were lower than those in the conventional group at the same time point(P<0.05),and TIR was higher than that in the conventional group at the same time point(P<0.05).After 6 months of intervention,the BG control rate in the personalized group was higher than that in the conventional group(P<0.05).Logistic regression analysis showed that the DM duration,exercise intervention methods and TIR were the influencing factors of BG control.Conclusions Exercise guidance is an effective intervention method to control diabetes.Compared with conventional exercise guidance,personalized exercise program has a better effect on controlling patients'BG level,and has a better effect on patients with short course of disease.

Objective To evaluate the value of 68Ga-DOTATATE and 18F-FDG PET/CT imaging in staging and treatment decision for gastroenteropancreatic neuroendocrine neoplasms(GEP-NEN).Methods This retrospective analysis was conducted in 49 patients with GEP-NEN undergoing 18F-FDG and 68Ga-DOTATATE PET/CT imaging at our hospital from August,2020 to March,2023,including 34 newly diagnosed patients and 15 patients with recurrence or metastasis after treatment.GEP-NEN were classified into G1,G2,and G3 neuroendocrine tumors(NET)and neuroendocrine carcinomas(NEC)based on pathological typing.The detection efficiency were classified into 4 patterns based on the number of positive tumor lesions detected by the two tracers:68Ga-DOTATATE>18F-FDG(A);68Ga-DOTATATE=18F-FDG(B);68Ga-DOTATATE<18F-FDG(C);and complementation(D).The value of dual-modality imaging in staging and treatment decision were evaluated by visual analysis.Results In the 49 patients with GEP-NEN,68Ga-DOTATATE PET/CT was superior to 18F-FDG PET/CT for detecting systemic tumor lesions(P<0.001)and more sensitive for detecting primary/recurrent lesions,lymph node metastasis,liver metastasis,and bone metastasis(P<0.05),while 18F-FDG PET/CT had higher detection rates for lung metastasis and peritoneal metastasis(P<0.05).In terms of the detection efficiency,Pattern A was found in 46.9%(23/49)patients,Pattern B in 38.8%(19/49),Pattern C in 12.2%(6/49),and Pattern D in 2.0%(1/49).The complementary value of 18F-FDG PET/CT to 68Ga-DOTATATE PET/CT was 0%in G1 NET patients(0/13),8.3%in G2 NET patients(2/24),50%in G3 NET patients(3/6),and 33.3%in NEC patients(2/6).12.2%(6/49)of the patients had their staging confirmed or changed due to additional lesions detected by 18F-FDG PET/CT imaging,resulting subsequently in establishment or adjustment of their treatment plans.Conclusion 68Ga-DOTATATE PET/CT imaging should be the primary choice for GEP-NEN patients.Additional 18F-FDG PET/CT imaging can potentially improve precision of staging and treatment decision-making for G2,G3 and NEC patients but provides virtually no clinical benefits for G1 NET patients.

Objective To investigate the influence of different cell structures on the static and dynamic mechanical performance of porous titanium alloy scaffolds,and to provide a theoretical mechanical basis for the application of scaffolds in the repair of mandibular bone defects.Methods Porous titanium alloy scaffolds with diamond,cubic,and cross-sectional cubic cell structures were manufactured using three-dimensional printing technology.Uniaxial compression tests and ratcheting fatigue with compression load tests were conducted to analyze the static and dynamic mechanical performances of scaffolds with different cell structures.Results The elastic moduli of the diamond cell,cross-sectional cubic cell,and cubic cell scaffolds were 1.17,0.566,and 0.322 GPa,respectively,and the yield strengths were 71.8,65.1,and 31.8 MPa,respectively.After reaching the stable stage,the ratcheting strains of the cross-sectional cubic,diamond,and cubic cell scaffolds were 3.3%,4.0%,and 4.5%,respectively.The ratcheting strain increased with increasing average stress,stress amplitude,and peak holding time,and decreased with increasing loading rate.Conclusions The evaluation results of the static mechanical performance showed that the diamond cell scaffold was the best,followed by the cross-sectional cubic cell scaffold and the cubic cell scaffold.The evaluation results of the dynamic mechanical performance showed that the cross-sectional cubic cell scaffold performed the best,followed by the diamond cell scaffold,whereas the cubic cell scaffold performed the worst.The fatigue performance of the scaffold is affected by the loading conditions.These results provide new insights for scaffold construction for the repair of mandibular bone defects and provide an experimental basis for further clinical applications of this scaffold technology.

Objective:To explore the effects of apigenin on apoptosis and hypoxia inducible factor-1α (HIF-1α)/nuclear factor κB (NF-κB) signaling pathway in renal cancer A498 cells.Methods:Human renal cell carcinoma A498 cells were cultured in vitro and divided into different concentrations of apigenin (10, 20, 40 μmol/L) groups, apigenin (40 μmol/L)+ HIF-1α agonist dimethylenediaminoacetic acid (DMOG) group, HIF-1α inhibitor rifiximab (YC-1) group, and control group. Cell proliferation was detected using cell counting kit-8 (CCK-8) assay and plate clone formation assay, apoptosis was detected using Hoechst 33258 staining and flow cytometry, and expression of apoptotic proteins and HIF-1/NF-B pathway proteins was detected using Western blot assay.Results:Celery extract significantly inhibited the proliferation of A498 cells, and the inhibitory effect was concentration dependent ( P<0.001). Compared with the control group, the apoptosis rates of A498 cells in the 10, 20, and 40 μmol/L apigenin groups and YC-1 groups were significantly increased [(4.35±1.04)% vs (10.06±1.13)%, (18.52±2.58)%, (32.17±2.63)%, (26.94±2.41)%], as well as the expression levels of B lymphocyte tumor 2 related protein (Bax) and Cleaved Caspase-3 protein, while the expression levels of B lymphocyte tumor 2 (Bcl-2) were significantly reduced (all P<0.001). Compared with the control group, the HIF-1α protein expression levels (0.85±0.08 vs 0.63±0.06, 0.31±0.03, 0.16±0.02) and p-NF-κB p65/NF-κB p65 ratio (0.82±0.08 vs 0.51±0.05, 0.30±0.03, 0.13±0.01) of A498 cells in the 10, 20, and 40 μmol/L apigenin groups were significantly reduced (all P<0.001). Compared with the apigenin group, the apoptosis rate of A498 cells in the apigenin+ DMOG group was significantly reduced [(32.17±2.63)% vs (14.85±1.62)%], and the expression levels of Bax and Cleared Caspase-3 proteins were significantly reduced, while the expression levels of Bcl-2 proteins were significantly increased (all P<0.001). Conclusions:Apigenin may promote apoptosis in renal cancer A498 cells by inhibiting the activation of the HIF-1α/NF-κB signaling pathway.

Objective:To investigate the clinical efficacy of Danggui Zicao ointment on diabetic pruritus caused by heat and wind in blood. Methods:A total of 197 patients with diabetic pruritus caused by heat and wind in blood who received treatment in Jinhua Hospital of Traditional Chinese Medicine from November 2020 to March 2022 were included in this randomized controlled study. They were randomly divided into a control group ( n = 99) and an observation group ( n = 98). Based on basic hypoglycemic treatment, the control group was given oral levocetirizine hydrochloride tablets, while the observation group was externally given Danggui Zicao ointment. Both groups were treated for 4 successive weeks. Pre- and post-treatment 12-Item Pruritus Severity Scale (12-PSS) score and clinical efficacy were compared between the two groups. Results:After 4 weeks of treatment, the 12-PSS score in each group significantly decreased compared with that before treatment ( t = 18.09, 11.31, both P < 0.05). The 12-PSS score in the observation group was (7.72 ± 1.64) points, which was significantly lower than (9.35 ± 2.18) points in the control group ( t = 3.52, P < 0.05). The total effective rate in the observation group was 87.8% (86/98), which was significantly higher than 76.8% (76/98) in the control group ( χ2 = 4.06, P < 0.05). Conclusion:Danggui Zicao ointment can effectively improve the clinical symptoms of patients with diabetic pruritus caused by heat and wind in blood, improve quality of life, and deserves clinical promotion.