1.Clinical characteristics and prognosis of carotid web-associated acute anterior circulation large vessel occlusion
Juntao YIN ; Li FENG ; Yanan JIA ; Xuemeng ZHAO ; Weiwei WANG ; Jing SUN ; Haikun LUO ; Yu WANG ; Tingting LIU ; Wan WANG ; Yuqing WEI
Chinese Journal of Neurology 2025;58(6):599-606
Objective:To investigate the clinical characteristics, prognosis, and the impact of different secondary prevention strategies on stroke recurrence in patients with carotid web (CaW)-associated acute anterior circulation large vessel occlusion (LVO).Methods:A retrospective analysis was conducted on 401 patients with acute anterior circulation LVO who underwent mechanical thrombectomy at 2 advanced stroke centers, Xingtai Central Hospital and Xingtai People′s Hospital, from January 2018 to June 2024. CaW was identified using digital subtraction angiography (DSA) and other imaging modalities. Based on the presence of CaW, patients were divided into CaW group and non-CaW group. Differences between the 2 groups in baseline characteristics, clinical features, and clinical outcomes were compared, and long-term follow-up was conducted for the CaW group.Results:Among the 401 patients, the CaW group consisted of 16 patients (4.0%), while the non-CaW group included 385 patients (96.0%). Compared to the non-CaW group, patients in the CaW group were younger [53 (46, 58) years vs 65 (56, 76) years, Z=-3.811, P<0.001], had a higher proportion of M1 segment middle cerebral artery occlusion [13/16 vs 54.0% (208/385), χ2=4.602, P=0.032] and a lower proportion of internal carotid artery terminus occlusion [1/16 vs 40.0% (154/385), χ2=6.024, P=0.014]; the 90-day modified Rankin Scale (mRS) score was significantly lower in the CaW group [1.00 (0, 1.75) vs 3.00 (1.00, 4.00), Z=14.210, P<0.001], and the proportion of patients with favorable functional independence (mRS score 0-2) was significantly higher [15/16 vs 45.7% (176/385), χ2=12.350, P<0.001] in the CaW group; the incidence of pneumonia in the CaW group was significantly lower [2/16 vs 42.6% (164/385), χ2=4.562, P=0.033]. Among the 16 CaW patients, 10 received antiplatelet therapy, 4 underwent carotid artery stenting (CAS), and 2 underwent carotid endarterectomy (CEA). During a median follow-up of 29 months, patients who underwent CAS and CEA had no stroke recurrence, while 2 patients who received antiplatelet therapy had stroke recurrence and subsequently underwent CAS and CEA. Conclusions:The proportion of CaW among patients with acute anterior circulation LVO was 4.0%. The patients with CaW were younger and had a higher proportion of M1 segment middle cerebral artery occlusion. Following mechanical thrombectomy, patients in the CaW group had good functional outcomes. Simple drug therapy may be insufficient to prevent stroke recurrence in CaW patients, and CAS and CEA may be effective therapeutic options.
2.Design and establishment of a database for toxins and molecular mass spectra of drugs
Xuemeng LI ; Mengfan LI ; Junjie MA ; Bin XU ; Jie DU ; Wei YOU ; Jia CHEN ; Jianwei XIE ; Dongsheng ZHAO
Military Medical Sciences 2025;49(1):41-46
Objective To construct a database for molecular mass spectra of toxins and drugs in order to facilitate the management and retrieval of mass spectra for nerve agents,metabolites and other small molecules.Methods Requirement analysis and functional design were performed using software engineering methods.The Spec2Vec algorithm was used for vector representation of mass spectra,while SMILES molecular structures were vectorized using the extended connectivity fingerprint(ECFP).A data storage model integrating structured information and vector representations was established using the Milvus database.Similarity search of mass spectra and molecular structures was conducted via vector similarity comparison and the FlashEntropySearch algorithm.Results The constructed database of mass spectra encompassed over 400,000 entries from such sources as OCAD,NIST,MASSBANK,metabolic products,and natural products of TCM,which was capable of searching for similarities in mass spectra and molecular structures.On a standard server,similarity search of mass spectra took no more than 5 seconds,while that of molecular structures took no more than 1 second.Conclusion The system enables efficient management of complex mass spectra and provides rapid retrieval and comparison of mass spectra-related information through advanced vector indexing technology,offering robust data support and research tools for toxicology and pharmacology.
3.Clinical characteristics and prognosis of carotid web-associated acute anterior circulation large vessel occlusion
Juntao YIN ; Li FENG ; Yanan JIA ; Xuemeng ZHAO ; Weiwei WANG ; Jing SUN ; Haikun LUO ; Yu WANG ; Tingting LIU ; Wan WANG ; Yuqing WEI
Chinese Journal of Neurology 2025;58(6):599-606
Objective:To investigate the clinical characteristics, prognosis, and the impact of different secondary prevention strategies on stroke recurrence in patients with carotid web (CaW)-associated acute anterior circulation large vessel occlusion (LVO).Methods:A retrospective analysis was conducted on 401 patients with acute anterior circulation LVO who underwent mechanical thrombectomy at 2 advanced stroke centers, Xingtai Central Hospital and Xingtai People′s Hospital, from January 2018 to June 2024. CaW was identified using digital subtraction angiography (DSA) and other imaging modalities. Based on the presence of CaW, patients were divided into CaW group and non-CaW group. Differences between the 2 groups in baseline characteristics, clinical features, and clinical outcomes were compared, and long-term follow-up was conducted for the CaW group.Results:Among the 401 patients, the CaW group consisted of 16 patients (4.0%), while the non-CaW group included 385 patients (96.0%). Compared to the non-CaW group, patients in the CaW group were younger [53 (46, 58) years vs 65 (56, 76) years, Z=-3.811, P<0.001], had a higher proportion of M1 segment middle cerebral artery occlusion [13/16 vs 54.0% (208/385), χ2=4.602, P=0.032] and a lower proportion of internal carotid artery terminus occlusion [1/16 vs 40.0% (154/385), χ2=6.024, P=0.014]; the 90-day modified Rankin Scale (mRS) score was significantly lower in the CaW group [1.00 (0, 1.75) vs 3.00 (1.00, 4.00), Z=14.210, P<0.001], and the proportion of patients with favorable functional independence (mRS score 0-2) was significantly higher [15/16 vs 45.7% (176/385), χ2=12.350, P<0.001] in the CaW group; the incidence of pneumonia in the CaW group was significantly lower [2/16 vs 42.6% (164/385), χ2=4.562, P=0.033]. Among the 16 CaW patients, 10 received antiplatelet therapy, 4 underwent carotid artery stenting (CAS), and 2 underwent carotid endarterectomy (CEA). During a median follow-up of 29 months, patients who underwent CAS and CEA had no stroke recurrence, while 2 patients who received antiplatelet therapy had stroke recurrence and subsequently underwent CAS and CEA. Conclusions:The proportion of CaW among patients with acute anterior circulation LVO was 4.0%. The patients with CaW were younger and had a higher proportion of M1 segment middle cerebral artery occlusion. Following mechanical thrombectomy, patients in the CaW group had good functional outcomes. Simple drug therapy may be insufficient to prevent stroke recurrence in CaW patients, and CAS and CEA may be effective therapeutic options.
4.Changes in muscle strength and pain in patients receiving Jianpi Yiqi Huoxue Formula after total knee arthroplasty
Jiaxin SHAN ; Yilong ZHANG ; Hongtao WU ; Jiayuan ZHANG ; Anan LI ; Wengang LIU ; Xuemeng XU ; Chuanxi ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(9):1378-1382
BACKGROUND:Some patients still have unsatisfactory improvement of operative limb fatigue and pain after total knee arthroplasty.Clinical findings show that Jianpi Yiqi Huoxue Formula can promote recovery after total knee arthroplasty,but the specific efficacy remains to be studied. OBJECTIVE:To observe the effect of Jianpi Yiqi Huoxue Formula on the muscle strength and pain of the operated limb after the primary unilateral total knee arthroplasty. METHODS:A total of 74 patients undergoing primary unilateral total knee arthroplasty were randomly divided into a trial group and a control group with 37 patients in each group.All patients received the same prostheses and surgical methods during the operation.Patients in the control group were treated with routine analgesics,anticoagulant drugs and functional exercise after the operation.The trial group received Jianpi Yiqi Huoxue Formula after the treatment in the control group.Both groups were treated continuously and followed up for 1 month.The changes in isokinetic muscle strength(peak torque and total work amount of extensor and flexor),visual analog scale score and the hospital for special surgery score of the two groups were analyzed. RESULTS AND CONCLUSION:(1)The trial group had better improvement in peak torque and total work amount of extensor and flexor and the hospital for special surgery score than the control group 14 days and 1 month after surgery(P<0.05).(2)In contrast to the control group,the visual analog scale score of the trial group improved better at 7 and 14 days and 1 month after surgery(P<0.05).(3)It is indicated that Jianpi Yiqi Huoxue Formula can effectively improve the muscle strength of the operated limb,enhance the degree of postoperative joint pain,and promote functional rehabilitation after total knee arthroplasty.
5.Clinical manifestations of 19 neonatal appendicitis cases
Haiyan WU ; Wendi HUANG ; Xuemeng LU ; Ming ZOU ; Yujuan ZHAO
Chinese Pediatric Emergency Medicine 2024;31(9):685-689
Objective:To study the clinical characteristics,diagnosis,treatment and prognosis of neonatal appendicitis.Methods:From January 2019 to December 2022,19 neonates with appendicitis(appendicitis group)and 38 neonates with sepsis(sepsis group)admitted to the Neonatal Department of Xi'an Children's Hospital Affiliated to Xi'an Jiaotong University were studied.The characteristics of clinical manifestation,imaging,treatment and prognosis of neonates in two groups were analyzed,retrospectively.Results:Among 19 neonates with appendicitis,31.6% were premature,the mean birth weight was(2 927.9±796.2)g,male∶female=2.17∶1.Abdominal distention(8/19,42.1%)and fever(8/19,42.1%)were the first symptoms of appendicitis,and the first symptoms of sepsis were mainly fever(20/38,52.6%)and poor reaction(7/38,18.4%).In the appendicitis group,the proportions of abdominal distension(89.5% vs. 5.3%),vomiting(36.8% vs. 2.6%),breast resistance(84.2% vs. 39.5%),mental reaction changing(94.7% vs. 71.1%)and abdominal positive signs(84.2% vs. 5.3%)were significantly higher than those in sepsis group( P<0.05).C-reactive protein(CRP)was elevated in 16 neonates with appendicitis and 13 neonates with sepsis,and elevated gradually in 14 neonates with appendicitis. Compared with sepsis group,CRP was higher in appendicitis group( P<0.05).Fifteen(78.9%)neonates with appendicitis were diagnosed only by ultrasound,mainly manifested as low echo area or liquid dark area in the right abdomen,thickening of the appendix wall or effusion in the cavity,and liquid exudation.Three(15.8%)neonates with appendicitis were diagnosed by ultrasound and CT.Eight(42.1%)neonates with appendicitis were complicated appendiceal perforation.Fifteen neonates with appendicitis were treated by conservative treatment,four cases were treated by operation,and all of them were cured and discharged. Conclusion:Abdominal ultrasonography should be improved as soon as possible in neonates with fever and septicemia,especially those with abdominal symptoms or signs,or CRP increased during treatment,and CT or surgical exploration if necessary,to confirm the diagnosis of neonatal appenditis and early treatment.
6.Diagnostic evaluation of non-invasive liver fibrosis models and establishment of a new model in chronic hepatitis B patients complicated with nonalcoholic fatty liver disease
Yinghui GAO ; Mingyue DENG ; Ruirui ZHU ; Zhixian GUO ; Jingya YAN ; Xuemeng ZHAO ; Zhiqin LI
Chinese Journal of Digestion 2024;44(10):686-692
Objective:To evaluate the diagnostic efficacy of FibroScan combined with various noninvasive diagnostic models for liver fibrosis in patients with chronic hepatitis B (CHB) complicated with nonalcoholic fatty liver disease (NAFLD), and to establish a new predictive model with common clinical indicators.Methods:From January 2016 to May 2024, the clinical data of 118 CHB patients complicated with NAFLD from the First Affiliated Hospital of Zhengzhou University, who underwent liver biopsy and FibroScan examination were respectively analyzed. According to the Scheuer scoring system, different diagnostic endpoints were set based on the degree of liver fibrosis (S0 to S1, ≥S2, ≥S3, and S4), fibrosis stage ≥S2 was designated as the criterion for significant liver fibrosis. Fibrosis-4 (FIB-4), γ-glutamyl transpeptidase (GGT) to platelet ratio (GPR), GGT-age-platelet-international normalized ratio (GAPI) model, S index, King index and Forns index were calculated according to the common clinical indicators. The independent t test or Mann-Whitney U test was used to compare the two groups. Spearman rank correlation was used to analyze the correlation between each noninvasive diagnostic method and the degree of liver fibrosis. Receiver operating characteristic curve (ROC) was plotted, and the DeLong test was performed to compare the area under the curve (AUC), and to evaluate the predictive value of FibroScan combined with various noninvasive diagnostic models for the diagnosis of liver fibrosis. The laboratory indicators were compared between patients with non-significant liver fibrosis and patients with significant liver fibrosis. And the indicators with statistically significant differences ( P<0.05) in the univariate analysis were further analyzed by multivariate logistic regression to establish a new predictive model for liver fibrosis. Hosmer-Lemeshow test was used to assess the model′s goodness of fit. Results:The results of Spearman rank correlation showed that FIB-4, GPR, FibroScan, GAPI model, S index, King index, and Forns index were positively correlated with the stage of liver fibrosis ( r=0.413, 0.458, 0.512, 0.473, 0.533, 0.380 and 0.478, all P<0.001). The results of ROC analysis indicated that among combination of FibroScan and other diagnostic models, the AUC values of FibroScan+ FIB-4, FibroScan+ Forns index were relatively high in ≥S2 and ≥S3, which were 0.804 and 0.907, respectively. The platelet count ((200.65±50.89)×10 9/L vs. (169.96±63.68)×10 9/L), total cholesterol ((4.69±0.77) mmol/L vs. (4.32±1.00) mmol/L), high-density lipoprotein (HDL) (1.28 (1.05, 1.46) mmol/L vs. 1.08 (0.92, 1.21) mmol/L), total protein (74.00 (70.63, 77.08) g/L vs. 68.80 (64.60, 73.55) g/L), albumin (47.06 (44.65, 48.81) g/L vs. 44.70 (41.55, 46.20) g/L), and globulin (26.80 (24.48, 29.70) g/L vs. 25.80 (23.05, 27.60) g/L) of the non-significant liver fibrosis group were higher than those of the significant liver fibrosis group, and the differences were statistically significant ( t=2.74, 2.09; Z=-3.30, -3.88, -3.95, -2.01; P=0.007, =0.040, =0.001, <0.001, <0.001, =0.044). GGT (27.50 (17.00, 41.75) U/L vs. 37.00 (22.50, 87.00) U/L), the liver stiffness measurement (LSM) in the non-significant hepatic fibrosis group was lower than the significant liver fibrosis group (6.85 (5.60, 9.26) kPa vs. 11.60 (7.08, 17.26) kPa), and the differences were statistically significant ( Z=-2.73, -4.39; P=0.006, <0.001). The result of multivariate logistic regression analysis revealed that globulin, albumin, HDL, and LSM were independent factors of liver fibrosis ( OR (95% confidence interval)=0.865 (0.759 to 0.985), 0.804 (0.691 to 0.935), 0.128 (0.023 to 0.711), and 1.251 (1.091 to 1.433), respectively; P=0.029, 0.025, 0.019, 0.001). A novel model, GLAH, was established with globulin, LSM, albumin, and HDL. The AUC for diagnosing liver fibrosis degree ≥S2, ≥S3, and S4 was 0.847, 0.938, and 0.909, respectively, which were higher than those of the above models. The positive predictive value for diagnosing liver fibrosis degree ≥S2 with GLAH>1.12 as the cutoff value was 95.8%. The negative predictive value for excluding fibrosis stage ≥S2 with GLAH<-1.41 was 92.3%. This approach could reduce the number of liver biopsies by 48.3% (57/118), with an accuracy of 94.7% (54/57). Conclusions:The clinical value of FibroScan combined with FIB-4 or Forns index is better in the diagnisis of fibrosis stage ≥S2 and ≥S3. The GLAH model has higher diagnostic value and can accurately predict the degree of liver fibrosis in CHB patients complicated with NAFLD, thus reducing the need for liver biopsy.
7.Diagnostic evaluation of non-invasive liver fibrosis models and establishment of a new model in chronic hepatitis B patients complicated with nonalcoholic fatty liver disease
Yinghui GAO ; Mingyue DENG ; Ruirui ZHU ; Zhixian GUO ; Jingya YAN ; Xuemeng ZHAO ; Zhiqin LI
Chinese Journal of Digestion 2024;44(10):686-692
Objective:To evaluate the diagnostic efficacy of FibroScan combined with various noninvasive diagnostic models for liver fibrosis in patients with chronic hepatitis B (CHB) complicated with nonalcoholic fatty liver disease (NAFLD), and to establish a new predictive model with common clinical indicators.Methods:From January 2016 to May 2024, the clinical data of 118 CHB patients complicated with NAFLD from the First Affiliated Hospital of Zhengzhou University, who underwent liver biopsy and FibroScan examination were respectively analyzed. According to the Scheuer scoring system, different diagnostic endpoints were set based on the degree of liver fibrosis (S0 to S1, ≥S2, ≥S3, and S4), fibrosis stage ≥S2 was designated as the criterion for significant liver fibrosis. Fibrosis-4 (FIB-4), γ-glutamyl transpeptidase (GGT) to platelet ratio (GPR), GGT-age-platelet-international normalized ratio (GAPI) model, S index, King index and Forns index were calculated according to the common clinical indicators. The independent t test or Mann-Whitney U test was used to compare the two groups. Spearman rank correlation was used to analyze the correlation between each noninvasive diagnostic method and the degree of liver fibrosis. Receiver operating characteristic curve (ROC) was plotted, and the DeLong test was performed to compare the area under the curve (AUC), and to evaluate the predictive value of FibroScan combined with various noninvasive diagnostic models for the diagnosis of liver fibrosis. The laboratory indicators were compared between patients with non-significant liver fibrosis and patients with significant liver fibrosis. And the indicators with statistically significant differences ( P<0.05) in the univariate analysis were further analyzed by multivariate logistic regression to establish a new predictive model for liver fibrosis. Hosmer-Lemeshow test was used to assess the model′s goodness of fit. Results:The results of Spearman rank correlation showed that FIB-4, GPR, FibroScan, GAPI model, S index, King index, and Forns index were positively correlated with the stage of liver fibrosis ( r=0.413, 0.458, 0.512, 0.473, 0.533, 0.380 and 0.478, all P<0.001). The results of ROC analysis indicated that among combination of FibroScan and other diagnostic models, the AUC values of FibroScan+ FIB-4, FibroScan+ Forns index were relatively high in ≥S2 and ≥S3, which were 0.804 and 0.907, respectively. The platelet count ((200.65±50.89)×10 9/L vs. (169.96±63.68)×10 9/L), total cholesterol ((4.69±0.77) mmol/L vs. (4.32±1.00) mmol/L), high-density lipoprotein (HDL) (1.28 (1.05, 1.46) mmol/L vs. 1.08 (0.92, 1.21) mmol/L), total protein (74.00 (70.63, 77.08) g/L vs. 68.80 (64.60, 73.55) g/L), albumin (47.06 (44.65, 48.81) g/L vs. 44.70 (41.55, 46.20) g/L), and globulin (26.80 (24.48, 29.70) g/L vs. 25.80 (23.05, 27.60) g/L) of the non-significant liver fibrosis group were higher than those of the significant liver fibrosis group, and the differences were statistically significant ( t=2.74, 2.09; Z=-3.30, -3.88, -3.95, -2.01; P=0.007, =0.040, =0.001, <0.001, <0.001, =0.044). GGT (27.50 (17.00, 41.75) U/L vs. 37.00 (22.50, 87.00) U/L), the liver stiffness measurement (LSM) in the non-significant hepatic fibrosis group was lower than the significant liver fibrosis group (6.85 (5.60, 9.26) kPa vs. 11.60 (7.08, 17.26) kPa), and the differences were statistically significant ( Z=-2.73, -4.39; P=0.006, <0.001). The result of multivariate logistic regression analysis revealed that globulin, albumin, HDL, and LSM were independent factors of liver fibrosis ( OR (95% confidence interval)=0.865 (0.759 to 0.985), 0.804 (0.691 to 0.935), 0.128 (0.023 to 0.711), and 1.251 (1.091 to 1.433), respectively; P=0.029, 0.025, 0.019, 0.001). A novel model, GLAH, was established with globulin, LSM, albumin, and HDL. The AUC for diagnosing liver fibrosis degree ≥S2, ≥S3, and S4 was 0.847, 0.938, and 0.909, respectively, which were higher than those of the above models. The positive predictive value for diagnosing liver fibrosis degree ≥S2 with GLAH>1.12 as the cutoff value was 95.8%. The negative predictive value for excluding fibrosis stage ≥S2 with GLAH<-1.41 was 92.3%. This approach could reduce the number of liver biopsies by 48.3% (57/118), with an accuracy of 94.7% (54/57). Conclusions:The clinical value of FibroScan combined with FIB-4 or Forns index is better in the diagnisis of fibrosis stage ≥S2 and ≥S3. The GLAH model has higher diagnostic value and can accurately predict the degree of liver fibrosis in CHB patients complicated with NAFLD, thus reducing the need for liver biopsy.
8.Clinical study on the application of guide catheter window guidance technology in intracranial artery stent angioplasty
Zhiyong LI ; Mengcai ZHANG ; Chunlin LI ; Peipei LIU ; Xuemeng ZHAO ; Lingtao TANG ; Yingyi LI ; Pengfei HU ; Yun WANG
Journal of Chinese Physician 2023;25(12):1849-1853
Objective:To explore the application value of guide tube fenestration and drainage technology in intracranial artery stenting surgery.Methods:A total of 120 patients with symptomatic intracranial atherosclerotic stenosis admitted to the Xingtai Third Hospital from January 2021 to December 2022 were selected and randomly divided into an observation group ( n=60) and a control group ( n=60). Both groups were treated with intracranial artery stenting, with the observation group receiving guidance catheterization and window opening technique during the surgery. Two groups of surgeries were observed and compared: the degree of vascular stenosis before and after surgery, the Montreal Cognitive Assessment Scale (MoCA) scores before and one month after surgery, intraoperative complications, and prognosis. Results:The surgical time and catheter placement time in the observation group were (110.20±23.32)minutes and (11.32±2.01)minutes, respectively, which were significantly shorter than those in the control group (all P<0.05). The stent placement rate and operation success rate in the observation group were 95.00% and 96.67%, respectively, significantly higher than those in the control group (all P<0.05). The degree of postoperative vascular stenosis in the observation group was (32.29±7.11)%, significantly milder than that in the control group [(44.43±8.15)%, P<0.05]. One month after surgery, the MoCA scores of both groups improved significantly compared to before surgery (all P<0.05), and there was no statistically significant difference between the groups ( P>0.05). There was no statistically significant difference in the incidence of collateral circulation occlusion and vascular rupture between the two groups (all P>0.05). During the follow-up period, there was no statistically significant difference in the incidence of restenosis, intracranial hemorrhage, and recurrent ischemic stroke between the observation group and the control group (all P>0.05); The good prognosis rate of the observation group was 73.33%, significantly higher than that of the control group (53.33%, P<0.05). Conclusions:The application of guided catheter fenestration technique in intracranial artery stenting has good value, which is beneficial for improving the stent placement rate and operation success rate, and improving the degree of vascular stenosis.
9.Molecular diagnosis and clinical features of 206 patients with 46, XY disorders of sexual development
Xuemeng LIU ; Shuangxia ZHAO ; Hui ZHU ; Bing HAN ; Yue XU ; Haijun YAO ; Yang LIU ; Yan CHEN ; Kaixiang CHENG ; Huaidong SONG ; Jie QIAO
Chinese Journal of Endocrinology and Metabolism 2022;38(9):781-788
Objective:To investigate methods of molecular diagnosis and clinical features of 46, XY disorders of sexual development(DSD).Methods:A total of 206 cases of 46, XY DSD patients, who visited the Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, from July 2009 to June 2021, underwent AA chip based on multiplex PCR and probe-capture-targeted next-generation sequencing. Clinical features of patients with genetic diagnosis were analyzed.Results:Among 206 patients, the diagnostic rate of patients with micropenis, hypospadias and cryptorchidism was the highest, up to 75.28%. Almost all patients had different degrees of undermasculinized external genitalia. The most frequent phenotype was micropenis with hypospadias(87.25%). Only one gene variant was detected in 81 patients(39.32%), multiple genetic variants were detected in 104 patients(50.49%), and no gene variant was identified in 21 patients(10.19%). 107 patients had definite genetic diagnosis, with a diagnostic rate of 51.94% by adding the pathogenic and likely pathogenic ratios following the American College of Medical Genetics and Genomics(ACMG) guidelines, including 40 patients of steroid 5α-reductase type 2(SRD5A2) variants(37.38%), 36 patients of androgen receptor(AR) variants(33.64%), 13 patients of steroidogenic factor 1(NR5A1) variants(16.82%), 6 patients of 17β-hydroxysteroid dehydrogenases 3(HSD17B3) variants(5.61%), 2 patients of 17α-hydroxylase/17, 20-lyase enzyme(CYP17A1), Wilms′ tumor 1(WT1) and GATA binding protein 4(GATA4) variants(1.87%), and one patient of luteinizing hormone receptor(LHCGR) variant(0.93%). Gynecomastia was found in 29 of 81 postpubertal patients, of which 25(86.21%) had AR variants.Conclusions:46, XY DSD presents complex clinical manifestations and molecular etiologies. Targeted nextgeneration sequencing has the advantages of high throughput, high efficiency and low cost, which has a high value especially in etiological diagnosis of 46, XY DSD with large genetic heterogeneity.
10.Clinical features and treatment outcome of four patients with Kallmann syndrome caused by fibroblast growth factor receptor-1 gene mutation
Yue XU ; Bing HAN ; Hui ZHU ; Fangqin XU ; Xuemeng LIU ; Wei LIU ; Jiannan LIN ; Shuangxia ZHAO ; Huaidong SONG ; Jie QIAO
Chinese Journal of Endocrinology and Metabolism 2021;37(5):447-452
Objective:To investigate the clinical features and treatment outcome of Kallmann syndrome(KS) caused by fibroblast growth factor receptor-1(FGFR1) gene mutation in 4 patients.Methods:Targeted next-generation sequencing(NGS) was performed on thirty KS and normosmic idiopathic hypogonadotropic hypogonadism(nIHH) patients. FGFR1 mutation was identified in four KS patients. The clinical data, laboratory and imaging examinations, and treatment outcome were retrospectively analyzed.Results:Four male patients, aging from 11 to 22 years old, presented as micropenis, and with olfactory dysfunction. Among them, two had history of cryptorchidism, three had history of cleft lip and palate repair surgery. The most severe patient presented with short stature, left microtia and dental agenesis. FGFR1 heterozygous mutation was identified in all four patients, two were point mutation(p.Y374X; p. E670K), and the other was frameshift mutation(p.S346Yfs*61; p.S723*fs*1). One patient, who started treatment of the pulsatile GnRH pump during his youth, succeeded in having two babies.Conclusion:Patients with Kallmann syndrome caused by FGFR1 mutation presents complex clinical manifestations. Besides dysosmia, micropenis, microrchidia, and delayed pubertal development are the main clinical manifestations in male patients. Symptoms such as cleft lip and palate are helpful for early recognition. Genotyping analysis is crucial to confirm the diagnosis. The pulsatile GnRH pump can produce satisfactory therapeutic effect, but the age of initiating therapy should be carefully considered.

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