To investigate the association between neutrophil to lymphocyte ratio (NLR) andestimated glomerular filtration rate (eGFR) in patients with diabetes using large-scale data.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Membranous nephropathy(MN)is the predominant cause of primary nephrotic syn-drome(NS)among adults.The identification of PLA2R as target antigen has brought about a pro-found transformation in the management of MN,offering a basis for the utilization of B-cell deplet-ing agents such as rituximab(RTX).The question of whether early intervention targeting antibodies can effectively impede the progression of MN,contrib-uting to enhanced disease control and long-term renal outcomes for patients,remains further explo-ration.We analyzed demographic data,laboratory parameters,and renal involvement in 13 patients with PLA2R antibody-related MN who received at least one RTX treatment at our center from Octo-ber 2019 to March 2023.Early-stage medium-to-high-risk MN was defined as baseline or admission anti-PLA2R antibody levels exceeding 50 RU/mL,ex-cluding patients who already presented with ne-phrotic syndrome at baseline.The median duration of MN at the initiation of the first RTX treatment was 4.1 months(IQR 1-7.7),and the median follow-up time after RTX therapy was 27 months(IQR 23-45).All patients had commenced renin-angiotensin system inhibitors before receiving RTX.Following RTX therapy,none of the 13 patients progressed to NS during the follow-up period,and 12 patients achieved complete or partial remission at the 2-year follow-up or the last visit.No deaths,severe infections,or other serious adverse reactions oc-curred during the follow-up period.In conclusion,RTX demonstrates favorable efficacy and safety in early-stage,medium-to-high-risk MN patients.Initi-ating antibody clearance therapy in these patients may be beneficial for long-term disease control and distant renal outcomes.

Objective: To compare the long-term outcomes of intersphincteric (trans-internal and external) sphincter resection (ISR) and abdominoperineal proctocolectomy (APR) for low-grade rectal cancer. Methods: We used a meta-analytic approach to compare these procedures . Published reports comparing ISR and APR for low rectal cancer in Pubmed, Medline, EMBASE and Cochrane, China Knowledge Network (CNKI), China Biomedical Literature Database, and Vipers databases between January 2005 and January 2023 were searched and those meeting the eligibility criteria were selected for extraction of data for analysis. Inclusion criteria were as follows: (1) all reports comparing ISR and APR for low rectal cancer before January 2023; and (2) prospective randomized controlled studies or well-designed cohort studies. Exclusion criteria were as follows: (1) full text not available; (2) duplicate publications, missing primary outcome indicators, and unknown data; and (3) invalid statistical analysis. Results: Sixteen studies with 2498 patients were included in this study. Compared with the APR group, patients in the ISR group were relatively younger (weighted mean difference [WMD]=-1.82, 95%CI=-2.94 to -0.70, P=0.01), had tumors farther from the anal verge (WMD=0.43, 95%CI=0.18 to 0.67, P<0.01), and lower pathological T-stage (T3-4 stage: OR=0.54, 95%CI=0.36 to 0.81, P<0.01). In contrast, there were no statistically significant differences between the two groups in gender (P=0.78), body mass index (P=0.77), or pathological N stage (P=0.09). Compared with the APR group, patients in the ISR group had a lower rate of postoperative complications (OR=0.77, 95%CI=0.60 to 0.99, P=0.04), shorter hospital stay (WMD=-4.30, 95%CI=-7.07 to -1.53, P<0.01), higher 5-year overall survival (HR=0.54, 95%CI=0.33 to 0.88, P=0.01), and higher 5-year disease-free survival (HR=0.65, 95%CI=0.47 to 0.90, P<0.01). Five-year locoregional failure (HR=0.66, 95%CI=0.40 to 1.10, P=0.11) and time to surgery (WMD=-9.71, 95%CI=-41.89 to 22.47, P=0.55) did not differ significantly between the two groups. Conclusion: ISR is a safe and effective alternative to APR for early-stage low-grade rectal cancer.
Humans ; Prospective Studies ; Rectal Neoplasms/pathology* ; Rectum/surgery* ; Proctectomy ; Anal Canal/pathology* ; Treatment Outcome

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To dynamically observe the levels and activities of von Willebrand factor (vWF) and ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in plasma of children with congenital ventricular septal defect (VSD) during perioperative period, and explore the value of plasma vWF antigen (vWF:Ag) and ADAMTS-13 activity (ADAMTS-13: AC) in evaluating vascular endothelial injury and prognosis in children with VSD. METHODS: In this cross-sectional study, a total of 74 children with VSD who underwent surgical treatment in TEDA International Cardiovascular Hospital from September 2018 to March 2019 were enrolled in the observation group. Among them, there were 28 cases of pure VSD, 32 cases of VSD combined with pulmonary hypertension, and 14 cases of VSD combined with valvular heart disease. 31 healthy children who underwent physical examination in Tianjin Children's Hospital during the same period were collected as the control group. The biochemical indexes of the children at admission were recorded. Peripheral plasma was collected at admission, postsurgery day 0 and day 1, respectively, and the levels of vWF activity (vWF:AC), vWF:Ag, ADAMTS-13 antigen (ADAMTS-13:Ag) and ADAMTS-13:AC were detected. RESULTS: The level of plasma vWF:Ag and vWF:AC in the observation group before surgery were significantly lower than those in the control group (P<0.001), and increased continuously, on postsurgery day 0 and day 1 (P<0.001). The level of ADAMTS-13:Ag in the observation group before surgery was significantly higher than that in the control group (P<0.001), which decreased significantly on postsurgery day 0 (P<0.001), and increased significantly on postsurgery day 1 compared with postsurgery day 0 (P=0.033). The level of ADAMTS-13:AC in the observation group before surgery was significantly lower than that in the control group (P=0.015), which decreased significantly on postsurgery day 0 (P=0.037), and increased on postsurgery day 1, but the difference was not statistically significant (P=0.051). The changes of vWF and ADAMTS-13 in the three subgroups were basically similar to the observation group. vWF: Ag/ADAMTS-13: AC ratio on postsurgery day 0 and day 1 had high diagnostic value in vascular endothelial injury (AUC=0.80, P<0.001; AUC=0.93, P<0.001). Preoperative vWF and ADAMTS-13 levels, and related baseline indicators were not correlated with postoperative infection, bleeding, thrombosis,etc. CONCLUSION Preoperative vWF: Ag, vWF: AC and ADAMTS-13: AC levels in children with VSD are low, while the level of ADAMTS-13: Ag is high. After surgery, the levels of vWF: Ag and vWF: AC are increased and the level of ADAMTS-13: Ag is decreased. The postoperative vWF: Ag/ADAMTS-13: AC ratio shows high diagnostic value in evaluating vascular endothelial injury. There is no correlation between preoperative vWF and ADAMTS-13 levels with perioperative clinical events.
Child ; Humans ; ADAMTS13 Protein ; Cross-Sectional Studies ; Heart Septal Defects, Ventricular ; Prognosis ; von Willebrand Factor

Objective: To analyze the short-term efficacy of sleeve gastrectomy plus uncut jejunojejunostomy (SG+uncut JJB) for patients with obesity. Methods: This prospective study was conducted in the General Surgery Department of Beijing Chaoyang Hospital from January to December 2020 (NCT04534504). The inclusion criteria were patients with a body mass index (BMI) of >32.5 kg/m², type 2 diabetes mellitus (T2DM) or at least two comorbidities with a BMI of 27.5-32.5 kg/m², a waist circumference of >90 cm (male) or >85 cm (female), and those aged between 16 and 65 years. The exclusion criteria included patients who were pregnant, diagnosed with severe neurological or mental illnesses, long-term users of antidepressants and immunosuppressants, and diagnosed with severe gastroesophageal reflux disease or underwent revision surgery. Patients with incomplete follow-up data or insufficient follow-up time were also excluded. Patients were divided into SG-uncut JJB group and SG group according to doctor's recommendation and patients' wills. The primary endpoint was the percentage of excess weight loss (%EWL), and the secondary endpoints were the percentage of total weight loss (%TWL) and the T2DM remission rate. All patients were regularly followed up until the end of December 2020. Results: After excluding seven patients who did not meet the inclusion criteria, 47 eligible patients were finally identified, with 21 in the SG+uncut JJB group and 26 in the SG group. The operation time (140 [110-180] minutes vs. 90 [70-180] minutes, Z=-3.642, P=0.001) and total cost ([54,000 ± 6000] yuan vs. [49,000 ± 7000] yuan, t=2.590, P=0.013) were slightly higher in the SG+uncut JJB group than in the SG group (all P<0.05). However, no significant differences were observed in terms of postoperative hospital stay, operative blood loss, and postoperative complications between the two groups (all P>0.05). The incidence of nausea and vomiting was significantly lower in the SG+uncut JJB group than in the SG group (9.5% [2/21] vs. 46.2% [12/26], χ²=7.453, P=0.006}. The %EWL and %TWL in the SG+uncut JJB group tended to increase gradually with time. The same trend was also observed in the SG group during the first 6 months of follow-up. The 12-month %EWL and %TWL in the SG group were slightly lower compared with the 6-month %EWL and %TWL (P=0.001). The 12-month %EWL values in the SG+uncut JJB and SG groups were (72.4%±12.3%) and (63.6%±25.7%), respectively. However, no significant differences were observed between the two groups in terms of %EWL. Moreover, the 1-month ([11.1%±2.4%] vs. [8.2%±4.4%], P=0.011) and 12-month %TWL ([29.7%±6.9%] vs. [20.3%±7.2%], P=0.001) were significantly higher in the SG+uncut JJB group than in the SG group. No significant differences were observed in terms of T2DM and hypertension remission (all P>0.05). Conclusion: SG+uncut JJB might achieve a promising weight-loss effect similar to SG with a relatively lower incidence of postoperative nausea and vomiting, and it might be an effective and safe approach for obesity management.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Diabetes Mellitus, Type 2/surgery* ; Gastrectomy ; Gastric Bypass ; Immunosuppressive Agents ; Laparoscopy ; Obesity/surgery* ; Obesity, Morbid/surgery* ; Prospective Studies ; Retrospective Studies ; Treatment Outcome ; Weight Loss

Objective: To compare the effects of three treatment options: emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery, on the pathological characteris- tics of surgically-resected specimens from patients with completely obstructive colorectal cancer. Methods: This was a retrospective cohort study analyzing clinicopathological data of patients with complete obstructive colorectal cancer who were admitted to the General Surgery Department of Beijing Chaoyang Hospital, Capital Medical University, between May 2012 and August 2020. The inclusion criteria were diagnosed with complete colorectal obstruction, pathologically confirmed as adenocarcinoma, resectable on imaging assessment, and without distant metastasis, combined with the patients' clinical manifestations and imaging examination findings. Patients with multiple colorectal cancers, refusal to undergo surgery, and concurrent peritonitis or intestinal perforation before stenting of the intestinal obstruction were excluded. Eighty-nine patients with completely obstructive colorectal cancer were enrolled in the study and were divided into emergency surgery group (n=30), stent-surgery group (n=34), and stent-neoadjuvant chemotherapy- surgery group (n=25) according to the treatment strategy. Differences in the pathological features (namely perineural infiltration, lymphovascular infiltration, tumor deposits, specimen intravascular necrosis, inflammatory infiltration, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cell ratio) and biomolecular markers (namely cluster of differentiation (CD)34, Ki67, Bcl-2, matrix metalloproteinase-9, and hypoxia-inducible factor alpha) were recorded. Pathological evaluation was based on the presence or absence of qualitative evaluation of pathological features, such as peripheral nerve infiltration, vascular infiltration, and cancer nodules within the specimens. The evaluation criteria for the pathological features of the specimens were as follows: Semi-quantitative graded evaluation based on the proportion of tissue necrosis, inflammatory infiltrates, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cells in the field of view within the specimen were classified as: grade 0: not seen within the specimen; grade 1: 0-25%; grade 2: 25%-50%; grade 3: 50%-75%; and grade 4: 75%-100%. The intensity of cellular immunity was classified as none (0 points), weak (1 point), moderate (2 points), and strong (3 points). The two evaluation scores were then multiplied to obtain a total score of 0-12. The immunohistochemical results were also evaluated comprehensively, and the results were defined as: negative (grade 0): 0 points; weakly positive (grade 1): 1-3 points; moderately positive (grade 2): 4-6 points; strongly positive (grade 3): 7-9 points; and very strong positive (grade 4): 10-12 points. Normally-distributed values were expressed as mean±standard deviation, and one-way analysis of variance was used to analyze the differences between the groups. Non-normally-distributed values were expressed as median (interquartile range: Q1, Q3). A nonparametric test (Kruskal-Wallis H test) was used for comparisons between groups. Results: The differences were not statistically significant when comparing the baseline data for age, gender, tumor site, American Society of Anesthesiologists score, tumor T-stage, N-stage, and degree of differentiation among the three groups (all P>0.05). The differences were not statistically significant when comparing the pathological characteristics of the resected tumor specimens, such as foreign body giant cells, inflammatory infiltration, and mucus lake formation among the three groups (all P>0.05). The rates of vascular infiltration were 56.6% (17/30), 41.2% (15/34), and 20.0% (5/25) in the emergency surgery, stent-surgery, and stent- neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences between the groups (χ²=7.142, P=0.028). Additionally, the rate of vascular infiltration was significantly lower in the stent-neoadjuvant chemotherapy-surgery group than that in the emergency surgery group (P=0.038). Peripheral nerve infiltration rates were 55.3% (16/30), 41.2% (14/34), and 16.0% (4/25), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (χ²=7.735, P=0.021). The infiltration peripheral nerve rates in the stent-neoadjuvant chemotherapy-surgery group were significantly lower than those in the emergency surgery group (P=0.032). The necrosis grade was 2 (1, 2), 2 (1, 3), and 2 (2, 3) in the emergency surgery, stent- surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=10.090, P=0.006). Post hoc comparison revealed that the necrosis grade was higher in the stent-surgery and stent-neoadjuvant chemotherapy-surgery groups compared with the emergency surgery group (both P<0.05). The abscess grade was 2 (1, 2), 3 (1, 3), and 2 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=6.584, P=0.037). Post hoc comparison revealed that the abscess grade in the emergency surgery group was significantly lower than that in the stent-surgery group (P=0.037). The fibrosis grade was 2 (1, 3), 3 (2, 3), and 3 (2, 3), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=11.078, P=0.004). Post hoc analysis revealed that the fibrosis degree was higher in both the stent-surgery group and the stent- neoadjuvant chemotherapy-surgery group compared with the emergency surgery group (both, P<0.05). The tumor cell ratio grades were 4 (3, 4), 4 (3, 4), and 3 (2, 4), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=8.594, P=0.014). Post hoc analysis showed that the tumor cell ratio in the stent-neoadjuvant chemotherapy-surgery group was significantly lower than that in the emergency surgery group (P=0.012). The CD34 grades were 2 (2, 3), 3 (2, 4), and 3 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, and the difference was statistically significant (H=9.786, P=0.007). Post hoc analysis showed that the CD34 grades in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups were 2 (2, 3), 3 (2, 4), and 3 (2,3), respectively. Post hoc analysis revealed that the CD34 concentration was higher in the stent-surgery group than that in the emergency surgery group (P=0.005). Conclusion: Stenting may increase the risk of distant metastases in obstructive colorectal cancer. The stent-neoadjuvant chemotherapy-surgery treatment model promotes tumor cell necrosis and fibrosis and reduces the proportion of tumor cells, vascular infiltration, and peripheral nerve infiltration, which may help decrease local tumor infiltration and distant metastasis in completely obstructive colorectal cancer after stent placement.
Humans ; Neoadjuvant Therapy/methods* ; Abscess ; Retrospective Studies ; Intestinal Obstruction/etiology* ; Stents ; Colorectal Neoplasms/therapy* ; Necrosis

Objective: To compare the efficacy and safety of prolonged dual antiplatelet therapy (DAPT>1 year) in patients with stable coronary artery disease (CAD) and diabetes who were event-free at 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) in a large and contemporary PCI registry. Methods: A total of 1 661 eligible patients were selected from the Fuwai PCI Registry, of which 1 193 received DAPT>1 year and 468 received DAPT ≤1 year. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding, MACCE was defined as a composite of all-cause death, myocardial infarction or stroke. Multivariate Cox regression analysis and inverse probability of treatment weighting (IPTW) Cox regression analysis were performed. Results: After a median follow-up of 2.5 years, patients who received DAPT>1 year were associated with lower risks of MACCE (1.4% vs. 3.2%; hazard ratio (HR) 0.412, 95% confidence interval (CI) 0.205-0.827) compared with DAPT ≤1 year, which was primarily caused by the lower all-cause mortality (0.1% vs. 2.6%; HR 0.031, 95%CI 0.004-0.236). Risks of cardiac death (0.1% vs. 1.5%; HR 0.051, 95%CI 0.006-0.416) and definite/probable ST (0.3% vs. 1.1%; HR 0.218, 95%CI 0.052-0.917) were also lower in patients received DAPT>1 year than those received DAPT ≤ 1 year. No difference was found between the two groups in terms of BARC type 2, 3, or 5 bleeding (5.3% vs. 4.1%; HR 1.088, 95%CI 0.650-1.821). Conclusions: In patients with stable CAD and diabetes who were event-free at 1 year after PCI with DES, prolonged DAPT (>1 year) provides a substantial reduction in ischemic cardiovascular events, including MACCE, all-cause mortality, cardiac mortality, and definite/probable ST, without increasing the clinically relevant bleeding risk compared with ≤ 1-year DAPT. Further well-designed, large-scale randomized trials are needed to verify the beneficial effect of prolonged DAPT in this population.
Coronary Artery Disease/therapy* ; Diabetes Mellitus, Type 2 ; Drug Therapy, Combination ; Drug-Eluting Stents ; Hemorrhage ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Risk Assessment ; Treatment Outcome

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*