【Objective】 To analyze the genetic variation characteristics and clinical phenotypes of a family with primary microcephaly (MCPH) caused by RTTN gene variation, and to provide reference for genetic counseling and prenatal diagnosis. 【Methods】 Clinical data of the three patients (including 2 fetuses and 2-year-old proband,and one fetus with clinical diagnosis) and their parents were collected and analyzed. Two of the children and their parents were tested by trio whole exome sequencing (trio-WES), sanger sequencing validation sites, and the hazard of their compound heterozygous variants was predicted. Literature review was conducted through domestic and international databases to collect reported RTTN gene mutation cases. 【Results】 Three patients in this family had anomalies of the septum pellucidum, hypoplasia of the corpus callosum and other brain malformations during fetal period. The proband (G2) and fetus (G3) showed intrauterine growth retardation and MCPH in late pregnancy; besides, G2 was born with global developmental delay. Trio-WES detected a c.2101(exon16)C>T(p.Arg701Ter,1526) nonsense and a c.2863(exon22)G>A(p.Glu955Lys)missense in the RTTN gene of G2 and G3, which were inherited from their father and mother, forming a compound heterozygous variant. According to the American College of Medical Genetics and Genomics (ACMG) variant classification guidelines, two variants were likely to be pathogenic (LP) and uncertain significance (VUS). Among them, c.2863(exon22)G>A was a newly discovered missense, which was predicted by the software to be harmful to the gene product. 【Conclusions】 Complex heterozygous variations of RTTN gene (c.2101C>T and c.2863G>A) are the genetic cause of MCPH in this family. This report has enriched the variation spectrum of RTTN gene, provided guidance for prenatal diagnosis and reproduction of this family, as well as material and reference for further understanding of the diseases caused by this gene mutation.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Objective:To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies.Methods:In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups.Results:The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ 2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ 2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ 2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ 2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ 2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ 2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ 2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ 2=5.442, P<0.001). HER-2 and Epstein–Barr virus positivity rates did not differ significantly between the two groups. Conclusion:Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

Objective To analyze the dosimetric advantages of CT-guided interstitial brachytherapy for recurrent cervical cancer. Methods A total of 16 patients with recurrent cervical cancer after radical surgery and adjuvant external beam radiotherapy received interstitial brachytherapy with CT-guided implantation of metal needles. The high-risk clinical target volume (HR-CTV) was given 36 Gy in 6 fractions.D90for HR-CTV in the brachytherapy and the cumulative D2 cm3values for the bladder,rectum,and sigmoid colon in the previous external beam radiotherapy and the brachytherapy were analyzed.Results The mean D90value for HR-CTV was 52.5±3.3 Gy. The cumulative D2 cm3values for the bladder, rectum, and sigmoid colon were 85.6±5.8 Gy,71.6±6.4 Gy,and 69.6±5.9 Gy,respectively.The mean number of metal needles was 6.1±1.5 in each brachytherapy. The actual 1-year overall survival and local control were 81% and 69%, respectively. Conclusions CT-guided interstitial brachytherapy for recurrent cervical cancer shows good dose-volume histogram parameters and few complications, so it may be clinically feasible. However,its long-term clinical efficacy needs further observation.

Objective To discuss the dosimetric advantage of computed tomography-guided interstitial brachytherapy compared with the conventional intracavitary brachytherapy for locally advanced cervical cancer,offering a more advantageous clinical treatment approach. Methods Twenty-eight locally advanced cervical cancer patients with bulky tumors ( tumor size>5 cm) after external beam radiotherapy received computed tomography-guided interstitial brachytherapy. Dosimetric outcomes of the current study, including the total dose ( external beam radiotherapy+ brachytherapy ) D90 for the HR-CTV and D2cc for the bladder,rectum, and sigmoid, were compared with a former patient group consisting of 30 patients who received the conventional intracavitary brachytherapy ( uterine tandem+ ovoid pairs ) . Results The mean D90 value for HR-CTV in the intracavitary brachytherapy group and interstitial brachytherapy group were (76.9±5. 7) and ( 88.1± 3. 3) Gy, respectively. The D2cc for the bladder, rectum, and sigmoid in the intracavitary brachytherapy group and interstitial brachytherapy group were (84.7±6. 8) Gy,(69.2±4. 2) Gy,(67.8±4. 5) Gy and (81.8±6. 5) Gy,(6.8±4. 0) Gy,(64.8±4. 1) Gy,respectively.1-year local tumor control rate in the intracavitary brachytherapy group and interstitial brachytherapy group were 59. 3％ and 85. 2％, respectively. Conclusions CT-guided interstitial brachytherapy shows a significant dosimetric advantage compared with the conventional intracavitary brachytherapy, and is, thereby, clinically possible feasible. However,the long term curative effect and toxicity need to be further investigated.

Objective To examine the dosimetric advantages of three-dimensional (3D) computed tomography (CT)-guided interstitial brachytherapy (BT) for target volume and surrounding normal tissue in patients with locally advanced cervical cancer,and to provide a simple and effective clinical treatment approach.Methods A total of 52 patients who had poor tumor response to external beam radiotherapy (EBRT) with a residual tumor greater than 5 cm at the time of BT were included.The patients were treated by 3D CT-guided interstitial BT using a hybrid applicator comprised of uterine tandem and free metal needles.The high-risk clinical target volume (HR-CTV),intermediate-risk clinical target volume (IR-CTV),and organs at risk (OAR) were contoured.The total dose,including external beam radiotherapy and high dose-rate BT,was biologically normalized to conventional 2 Gy fractions (EQD2).D90and D100for both HR-CTV and IR-CTV,and D2 ccfor the bladder,rectum,and sigmoid were analyzed.Results The mean D90value for HR-CTV was 88.4±3.5 Gy.The D2 ccfor the bladder,rectum,and sigmoid were 81.1±5.6,65.7±5.1,and 63.1±5.4 Gy,respectively.D2 cc≤90 Gy for the bladder and D2 cc≤70 Gy for the sigmoid were observed in all the patients.D2 cc≤70 Gy for the rectum was observed in 89% of patients.Conclusions 3DCT-guided interstitial BT has a significant dosimetric advantage for target volume accompanied by few minor complications,and thereby may be clinically feasible for treating locally advanced cervical cancer.However,its long-term efficacy and possible toxicities will require further clinical observation.

Objective To investigate the relationship between ischemic time and thrombus types in patients with ST-segment elevation myocardial infarction (STEMI).Methods Eighty-two STEMI patients undergone emergency percutaneous coronary intervention (PCI) and coronary thrombus aspiration (CTA) from Sep.2012 to Apr.2016 were included and divided into 3 groups according to the ischemic time:≤4 hours (n=36),4-7 hours (n=30) and ＞7 hours (n=16).Visible aspirated thrombi were collected and separated into erythrocyte-rich type,platelet/fibrin-rich type and combined type thrombi by HE dying.The percentage difference of the 3 types thrombi was compared among the 3 groups.Results The percentage of platelet/fibrinrich type,erythrocyte-rich type and combined type thrombi in the 3 groups were as follows:in ≤4h group:61.1％(22/36),8.3％(3/36) and 30.6％(11/36),P=0.019;in 4-7h group:23.3％(7/30),10.0％(3/30) and 66.7％(20/30),P=0.012;and in ＞7h group:43.8％(7/16),12.5％(2/16) and 43.8％(7/16),P=0.913.For platelet/fibrin-rich type thrombi,the percentages in 3 periods were 61.1％(22/36),19.4％(7/36) and 19.4％(7/36),P=0.009;For combined type thrombi,the percentages in 3 periods were 28.9％(11/38),52.6％(20/38) and 18.4％(7/38),P=0.013;For erythrocyte-rich type thrombi,the percentages in 3 periods were 37.5％(3/8),37.5％(3/8) and 25.0％(2/8),P=0.895.Conclusions The types of intracoronary aspirated thrombi differ from various periods.Ischemia time may be an important predicted factor.

Objective To study the effect,safety and quality of life of different operation opportunity on the patients with ureteral calculi after extracorporeal shock wave lithotripsy.Methods From July 2015 to September 2016,45 patients with ureteral calculi who received lithotomy after 2 times of extracorporeal shock wave lithotripsy (ESWL) in our hospital were selected as observation group.Another 45 cases who received more than 3 times of ESWL and turend to lithotomy at the same period were selected as control group.The clinical effect was compared between the two groups.Results The total effective rate of the observation group was 95.56％ (43/45),which was significantly higher than 71.11％ (32/45) of the control group,the difference was statistically significant (χ2=9.680;P=0.002).The incidence rates of obstruction(17.78％),infection (26.67％) and hydronephrosis (24.44％) in the observation group were significantly lower than those in the control group (42.22％,64.44％ and 60.00％),the differences were statistically significant (χ2=6.402,12.947,11.660;P=0.011,0.000,0.001).The scores of diet [(83.2±12.6)points],spirit[(85.6±13.3)points],sleep[(87.3±15.4)points] and psychological score[(85.9±13.6)points] in the observation group were significantly higher than those of the control group [(75.1±11.4)points,(76.2±11.6)points,(77.4±13.2)points and (73.2±10.7)points],the differences were statistically significant (t=3.003,4.038,3.514,4.513;P=0.004,0.000,0.001,0.000).The satisfaction rate of patients(97.78％) of the observation group was significantly higher than 77.78％ of the control group,the difference was statistically significant (χ2=8.389;P=0.004).Conclusion Patients with ureteral calculi who received more than 2 times of ESWLand the stones in the body has not been effectively removed,should be accepted as soon as possible stone surgery treatment,it can improve the clinical effect,reduce the incidence of complications,improve the quality of life of patients.

Objective: To investigate the impact of symptom onset to first medical contact (SO-to-FMC)time on the prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI). Methods: The clinical data of 341 consecutive STEMI patients, who were hospitalized to our hospital and received primary percutaneous coronary intervention(PCI) from August 2011 to April 2016, were retrospectively analyzed. The patients were divided into ≤90 min group (201 cases) and >90 min group (140 cases) according to the SO-to-FMC time. The treatment time, mortality and incidence of major adverse cardiac and cerebro-vascular events(MACCE) were analyzed. The risk factor of 1-year mortality after PCI and 1-year incidence of MACCE during the post-discharge follow-up period were analyzed by binary logistic regression analysis. The predictor of 4.5-year mortality after PCI was analyzed by multivariate Cox regression analysis. Methods The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P=0.023), first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001)were all significantly shorter in the ≤90 min group than in>90 min group. The 30-day mortality (2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89 (5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post-discharge follow-up period(1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year cumulative mortality(3.00% vs. 11.20%, P=0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results: The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P=0.023) , first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001) were all significantly shorter in the ≤90 min group than in >90 min group. The 30-day mortality(2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89(5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post-discharge follow-up period (1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year cumulative mortality (3.00% vs. 11.20%, P=0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results of binary logistic regression analysis showed that the SO-to-FMC time >90 min was the risk factor of 1-year mortality(OR=2.90, 95%CI 1.22-6.92, P=0.016) and 1-year incidence of MACCE (OR=5.19, 95%CI 1.21-22.20, P=0.026) during the post-discharge follow-up period. Multivariate Cox regression analysis demonstrated that the SO-to-FMC time >90 min was the risk factor of 4.5-year mortality after PCI in patients with STEMI (HR=2.88, 95%CI 1.10-7.53, P=0.031). Conclusion Shorting the SO-to-FMC time can significantly reduce the treatment time of STEMI patients, short and long-term mortalities and the incidence of MACCE, and improve the prognosis of patients with STEMI.

Objective Compare the efifcacy and safety of drug eluting stent (DES) for treatment of in stent restenosis (ISR) and coronary de novo lesions. Methods Patients treated with DES for ISR and de novo lesions in Beijing Anzhen Hospital between October 2008 and December 2011 were followed up for 1 year. All lesions were divided into ISR and de novo group. Major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI) and clinical target lesion revascularization (TLR) were the primary endpoints. Results The study population consisted of 204 patients in the ISR group and 494 patients in the de novo group. Baseline clinical and angiographic parameters were comparable between the two groups. The rate of diabetic was higher in the ISR group than that in the de novo group (36.6%to 27.1%, P < 0.05). The diameter of coronary artery was smaller in the ISR group than that in the de novo group (2.72±0.36 to 3.08±0.54, P<0.01). The rate of TLR in the ISR group was higher than that in the de novo group (10.7%to 17.2%, P<0.05;14.2%to 21.1%, P<0.05),contributing to higher MACE in ISR group. Conclusions DES implantation is safe and effective for treatment of ISR lesions, but the rate of TLR is higher compared to treatment of de novo lesions.