Objective:To analyze the relationship between clinicopathological features and germline mismatch repair (MMR) gene variants in endometrial cancer patients and to evaluate the clinical utility of germline multi-gene panel testing.Methods:This single-center, retrospective case series study included 100 endometrial cancer patients treated in Zhongshan Hospital, Fudan University between July 2022 and February 2024. We collected clinicopathological data and tumor molecular testing results. 61 cancer susceptibility genes were tested using next-generation sequencing, and the associations between the detection rate of germline variants and the clinicopathological characteristics in endometrial cancer patients were explored.Results:Among 100 patients, 28% (28/100) were found to have pathogenic variants in cancer susceptibility genes, of which 20 patients carried germline MMR gene variants and the remaining 8 patients carried variants in other cancer susceptibility genes. Of the 20 patients diagnosed with Lynch syndrome, only 40% (8/20) met the Chinese family history criteria for Lynch syndrome. Among 53 patients with intact MMR protein expression, 1 patient was identified with a germline MMR gene variant. In the 14 Lynch syndrome patients with confirmed microsatellite status, 5/14 of those showed low microsatellite instability or microsatellite stability. Germline multi-gene panel testing in all endometrial cancer patients additionally identified 1 Lynch syndrome patient and 8 patients with non-Lynch hereditary cancers.Conclusion:Current clinical screening criteria may miss some endometrial cancer patients with Lynch syndrome. Compared with traditional screening pattern, germline multi-gene panel testing not only improves the detection rate of Lynch syndrome in endometrial cancer patients but also identifies other hereditary cancer predispositions.

Objective:? To summarize the achievements in improving the consistency of clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing results.Methods:? From 2021 to 2024, Zhongshan Hospital Affiliated to Fudan University recruited laboratories voluntarily participating in the MSHP (Clinical LC-MS/MS Testing Consistency Program). As of Batch 202404, a total of 76 laboratories had enrolled, including 60 medical institutions (all tertiary hospitals) and 16 third-party laboratories. Test items were established, and comparative samples were distributed regularly-each item′s samples covered three concentrations (high, medium, and low). Samples were shipped via cold chain and tested within one week. Our laboratory′s measurements served as the target, with participating labs′ results within ±25% of the target deemed qualified. Passing-Bablok regression and Bland-Altman analysis were used to assess consistency.Results:Taking 3-MT (3-methoxytyramine) as an example, the coefficients of variation (CVs) for the project′s three concentration levels improved from 17.00%, 47.18%, and 4.88% in the first comparative batch to 9.59%, 9.59%, and 6.1% in Batch 202404. Passing-Bablok regression results for the 5 units participating in 3-MT testing showed that Laboratory A had proportional bias but no systematic bias (regression slope [95% CI]: 0.903 [0.862-0.952]; intercept [95% CI]: 0.912 [-1.921-6.073]). The remaining laboratories exhibited no proportional or systematic bias with the target (Laboratory B: slope 1.031 [0.961-1.147], intercept-0.733 [-4.641-8.272]; Laboratory C: slope 0.982 [0.940-1.009], intercept-0.576 [-2.675-1.891]; Laboratory D: slope 0.973 [0.939-1.066], intercept-1.168 [-6.108-1.649]; Laboratory E: slope 0.999 [0.905-1.051], intercept-1.876 [-6.111-3.508]). Bland-Altman analysis indicated that all 5 laboratories′ results generally showed good consistency with the target. Through quality feedback and optimizing sample preparation concentrations, result consistency was enhanced.? Conclusion:? Clinical LC-MS/MS testing consistency programs contribute to improving the comparability of test results.

Objective To examine the significance of susceptible gene detection for hereditary cancer syndrome (HCS) among general population. Methods A total of 2 928 individuals undergoing routine health examinations in Healthcare Center of Zhongshan Hospital, Fudan University, from September 2021 to April 2024 were enrolled retrospectively. Next generation sequencing was employed to identify susceptible genes for HCS. American College of Medical Genetics and Genomics (ACMG) guideline was used to analyze the pathogenicity of variants. Clinical data, imagings, follow-up data were also collected. Results The overall mutation rate of HCS panel was 3.59% (105/2 928), with 0.61% (18/2 928) for MutY DNA glycosylase (MUTYH), 0.27% (8/2 928) for breast cancer susceptibility gene 1/2 (BRCA1/2) and 0.23% (7/2 928) for mismatch repair (MMR) genes. Conclusions Healthy individuals carrying tumor susceptible genes usually lack the relevant clinical phenotypes. Whether comprehensive testing needs to be carried out among healthy people remains to be further explored.

Objective To investigate the value of low tube voltage and low dose contrast agents combined with artificial intelligence iterative reconstruction(AIIR)in upper limb CT angiography(CTA)for displaying arteriovenous fistula(AVF).Methods Totally 65 patients with chronic renal failure and suspected AVF stenosis who underwent upper limb CTA were prospectively enrolled and randomly divided into conventional-dose group(CD group,n=30)and low-dose group(LD group,n=35).In CD group,CTA was acquired using conventional tube voltage(100 kVp)and contrast agents dosage(1.0 ml/kg body mass),and conventional hybrid iterative reconstruction(HIR)was used to reconstruct images(group A),while in LD group,CTA was collected using 80 kVp and contrast agent dosage of 0.6 ml/kg body mass,and images were reconstructed with HIR(group B)and AIIR(group C),respectively.Then subjective and objective assessment of imaging quality were performed,respectively,the results were compared among groups,while the radiation dose and dosage of contrast agents were compared between CD and LD groups.Results No significant difference of subjective score of imaging quality nor confidence for diagnosing AVF stenosis was found between group A and group C(both P＞0.017),and all the above scores were higher than those in group B(all P＜0.017).Signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of subclavian artery,brachial artery and radial artery in group C were all higher than those in groups A and B(all P＜0.017),while no significant difference of SNR nor CNR was found between group A and B(all P＞0.017).The volume CT dose index,dose length product and dosage of contrast agent in LD group were all lower than those in CD group(all P＜0.001).Conclusion Low tube voltage and low dose contrast agents combined with AIIR in upper limb CTA for displaying AVF could reduce radiation dose and contrast agents dosage under the condition of ensuring imaging quality.

Objective:To analyze the relationship between clinicopathological features and germline mismatch repair (MMR) gene variants in endometrial cancer patients and to evaluate the clinical utility of germline multi-gene panel testing.Methods:This single-center, retrospective case series study included 100 endometrial cancer patients treated in Zhongshan Hospital, Fudan University between July 2022 and February 2024. We collected clinicopathological data and tumor molecular testing results. 61 cancer susceptibility genes were tested using next-generation sequencing, and the associations between the detection rate of germline variants and the clinicopathological characteristics in endometrial cancer patients were explored.Results:Among 100 patients, 28% (28/100) were found to have pathogenic variants in cancer susceptibility genes, of which 20 patients carried germline MMR gene variants and the remaining 8 patients carried variants in other cancer susceptibility genes. Of the 20 patients diagnosed with Lynch syndrome, only 40% (8/20) met the Chinese family history criteria for Lynch syndrome. Among 53 patients with intact MMR protein expression, 1 patient was identified with a germline MMR gene variant. In the 14 Lynch syndrome patients with confirmed microsatellite status, 5/14 of those showed low microsatellite instability or microsatellite stability. Germline multi-gene panel testing in all endometrial cancer patients additionally identified 1 Lynch syndrome patient and 8 patients with non-Lynch hereditary cancers.Conclusion:Current clinical screening criteria may miss some endometrial cancer patients with Lynch syndrome. Compared with traditional screening pattern, germline multi-gene panel testing not only improves the detection rate of Lynch syndrome in endometrial cancer patients but also identifies other hereditary cancer predispositions.

Objective:? To summarize the achievements in improving the consistency of clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing results.Methods:? From 2021 to 2024, Zhongshan Hospital Affiliated to Fudan University recruited laboratories voluntarily participating in the MSHP (Clinical LC-MS/MS Testing Consistency Program). As of Batch 202404, a total of 76 laboratories had enrolled, including 60 medical institutions (all tertiary hospitals) and 16 third-party laboratories. Test items were established, and comparative samples were distributed regularly-each item′s samples covered three concentrations (high, medium, and low). Samples were shipped via cold chain and tested within one week. Our laboratory′s measurements served as the target, with participating labs′ results within ±25% of the target deemed qualified. Passing-Bablok regression and Bland-Altman analysis were used to assess consistency.Results:Taking 3-MT (3-methoxytyramine) as an example, the coefficients of variation (CVs) for the project′s three concentration levels improved from 17.00%, 47.18%, and 4.88% in the first comparative batch to 9.59%, 9.59%, and 6.1% in Batch 202404. Passing-Bablok regression results for the 5 units participating in 3-MT testing showed that Laboratory A had proportional bias but no systematic bias (regression slope [95% CI]: 0.903 [0.862-0.952]; intercept [95% CI]: 0.912 [-1.921-6.073]). The remaining laboratories exhibited no proportional or systematic bias with the target (Laboratory B: slope 1.031 [0.961-1.147], intercept-0.733 [-4.641-8.272]; Laboratory C: slope 0.982 [0.940-1.009], intercept-0.576 [-2.675-1.891]; Laboratory D: slope 0.973 [0.939-1.066], intercept-1.168 [-6.108-1.649]; Laboratory E: slope 0.999 [0.905-1.051], intercept-1.876 [-6.111-3.508]). Bland-Altman analysis indicated that all 5 laboratories′ results generally showed good consistency with the target. Through quality feedback and optimizing sample preparation concentrations, result consistency was enhanced.? Conclusion:? Clinical LC-MS/MS testing consistency programs contribute to improving the comparability of test results.

Objective To investigate the value of low tube voltage and low dose contrast agents combined with artificial intelligence iterative reconstruction(AIIR)in upper limb CT angiography(CTA)for displaying arteriovenous fistula(AVF).Methods Totally 65 patients with chronic renal failure and suspected AVF stenosis who underwent upper limb CTA were prospectively enrolled and randomly divided into conventional-dose group(CD group,n=30)and low-dose group(LD group,n=35).In CD group,CTA was acquired using conventional tube voltage(100 kVp)and contrast agents dosage(1.0 ml/kg body mass),and conventional hybrid iterative reconstruction(HIR)was used to reconstruct images(group A),while in LD group,CTA was collected using 80 kVp and contrast agent dosage of 0.6 ml/kg body mass,and images were reconstructed with HIR(group B)and AIIR(group C),respectively.Then subjective and objective assessment of imaging quality were performed,respectively,the results were compared among groups,while the radiation dose and dosage of contrast agents were compared between CD and LD groups.Results No significant difference of subjective score of imaging quality nor confidence for diagnosing AVF stenosis was found between group A and group C(both P＞0.017),and all the above scores were higher than those in group B(all P＜0.017).Signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of subclavian artery,brachial artery and radial artery in group C were all higher than those in groups A and B(all P＜0.017),while no significant difference of SNR nor CNR was found between group A and B(all P＞0.017).The volume CT dose index,dose length product and dosage of contrast agent in LD group were all lower than those in CD group(all P＜0.001).Conclusion Low tube voltage and low dose contrast agents combined with AIIR in upper limb CTA for displaying AVF could reduce radiation dose and contrast agents dosage under the condition of ensuring imaging quality.

Objective:The aim of this study was to develop and validate a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of melatonin in human serum.Methods:We describe the performance and validation of melatonin by LC-MS/MS. 182 serum samples from the patients diagnosed with Sleep disturbance who visited the Department of Psychiatry at Zhongshan Hospital affiliated to Fudan University from February 2022 to March 2023(56 males,162 females,mean age [45.51±16.31]years), as well as 182 healthy individuals were included(87 males,95 females,mean age [48.55±11.93]years). The two groups were used to assess the application of serum melatonin levels as a diagnostic indicator for sleep disorders (SDs). The liquid chromatography mass spectrometry (LC-MS) system with an chromatography column (2.1×100 mm, 1.8 μm) was used for separation. The column temperature was set at 35 ℃, as well as the mobile phase consisting of a 0.1% formic acid aqueous solution and pure acetonitrile. The flowing rate was set at 0.4 ml/min for gradient elution. The LC-MS/MS method was validated according to guidance documents, including the following parameters: specificity, selectivity, matrix effect, carryover contamination and reproducibility, lower limit of measuring interval, linearity, precision, recovery rate, dilution consistency, and serum sample stability. Then, it was subsequently employed to profile melatonin changes in Sleep disturbance.Results:The lower limit of quantification for melatonin was 1 pg/ml, and the linear range of detection was 1 pg/ml to 500 pg/ml ( r=0.999). The intra-day and intra-batch precision, expressed as the coefficient of variation ( CV), was within the range from 3.07% to 6.86%, which met the requirement of less than 15%. The recovery rate of the spiked samples ranged from 105.91% to 116.30%. The level of serum melatonin in the sleep disturbance group was significantly lower than that in the healthy control group ([2.00(1.00,3.28)] vs [8.35(4.28,14.80)] pg/ml, P<0.001). Conclusions:The LC-MS/MS method we developed for the quantification of melatonin is clinical practicable.

Objective:To investigate the embryo development and clinical pregnancy outcomes in patients with ovarian hyperstimulation syndrome (OHSS) undergoing assisted reproductive technology (ART).Methods:A retrospective cohort study was conducted on data from 4 080 cycles of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatments performed at the Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University from August 2019 to August 2021. Patients were divided into OHSS group ( n=524) and non-OHSS group (control group, n=3 556) based on whether OHSS occurred, and the OHSS group was further divided into OHSS combined with polycystic ovary syndrome (PCOS) subgroup ( n=231) and OHSS combined with non-PCOS subgroup ( n=293) based on the presence of PCOS. General information, embryo developmental data and clinical outcomes were compared between the two groups. Results:1) Patients in the OHSS group [(30.7±3.6) years] were younger than those in control group [(31.5±4.8) years, P<0.001], and the number of retrieved oocytes (28.2±5.7), rates of high-quality embryos [52.7% (4 982/9 463)], blastocyst formation [54.0% (5 059/9 371)], biochemical pregnancy [75.0% (393/524)], clinical pregnancy [69.5% (364/524)], and live birth [58.0% (304/524)] were significantly higher in the OHSS group than in control group [12.5±6.7, 49.8% (14 042/28 204), 51.4% (14 279/27 797), 59.5% (2 115/3 556), 54.1% (1 924/3 556), 43.6% (1 550/3 556), respectively; all P<0.001]. 2) Patients in the OHSS combined with PCOS subgroup [(30.2±3.1) years] were younger than those in the OHSS combined with non-PCOS subgroup [(31.1±4.0) years, P=0.009], and the estradiol level [165.0 (101.0, 222.5) pmol/L] was higher than that in the OHSS combined with non-PCOS subgroup [141.0 (81.0,202.0) pmol/L, P=0.005]; rates of high-quality embryos [56.3% (2 413/4 284)], blastocyst formation [67.1% (2 846/4 239)], and high-quality blastocysts [57.7% (2 445/4 239)] were also significantly higher in the OHSS combined with PCOS subgroup than in the OHSS combined with non-PCOS subgroup [49.6% (2 569/5 179), 60.3% (3 092/5 132), 50.9% (2 614/5 132), respectively; all P<0.001]. Conclusion:There is a certain correlation between OHSS and female age. The occurrence of OHSS does not affect embryo development and does not increase adverse pregnancy outcomes in infertile patients. The presence of PCOS does not affect the pregnancy outcomes of OHSS patients. However, in ART, we still strive to avoid the occurrence of adverse events such as OHSS as much as possible.

Objective:To investigate the embryo development and clinical pregnancy outcomes in patients with ovarian hyperstimulation syndrome (OHSS) undergoing assisted reproductive technology (ART).Methods:A retrospective cohort study was conducted on data from 4 080 cycles of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatments performed at the Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University from August 2019 to August 2021. Patients were divided into OHSS group ( n=524) and non-OHSS group (control group, n=3 556) based on whether OHSS occurred, and the OHSS group was further divided into OHSS combined with polycystic ovary syndrome (PCOS) subgroup ( n=231) and OHSS combined with non-PCOS subgroup ( n=293) based on the presence of PCOS. General information, embryo developmental data and clinical outcomes were compared between the two groups. Results:1) Patients in the OHSS group [(30.7±3.6) years] were younger than those in control group [(31.5±4.8) years, P<0.001], and the number of retrieved oocytes (28.2±5.7), rates of high-quality embryos [52.7% (4 982/9 463)], blastocyst formation [54.0% (5 059/9 371)], biochemical pregnancy [75.0% (393/524)], clinical pregnancy [69.5% (364/524)], and live birth [58.0% (304/524)] were significantly higher in the OHSS group than in control group [12.5±6.7, 49.8% (14 042/28 204), 51.4% (14 279/27 797), 59.5% (2 115/3 556), 54.1% (1 924/3 556), 43.6% (1 550/3 556), respectively; all P<0.001]. 2) Patients in the OHSS combined with PCOS subgroup [(30.2±3.1) years] were younger than those in the OHSS combined with non-PCOS subgroup [(31.1±4.0) years, P=0.009], and the estradiol level [165.0 (101.0, 222.5) pmol/L] was higher than that in the OHSS combined with non-PCOS subgroup [141.0 (81.0,202.0) pmol/L, P=0.005]; rates of high-quality embryos [56.3% (2 413/4 284)], blastocyst formation [67.1% (2 846/4 239)], and high-quality blastocysts [57.7% (2 445/4 239)] were also significantly higher in the OHSS combined with PCOS subgroup than in the OHSS combined with non-PCOS subgroup [49.6% (2 569/5 179), 60.3% (3 092/5 132), 50.9% (2 614/5 132), respectively; all P<0.001]. Conclusion:There is a certain correlation between OHSS and female age. The occurrence of OHSS does not affect embryo development and does not increase adverse pregnancy outcomes in infertile patients. The presence of PCOS does not affect the pregnancy outcomes of OHSS patients. However, in ART, we still strive to avoid the occurrence of adverse events such as OHSS as much as possible.