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.

To evaluate the analytical performance of a specific IgE (sIgE) quantitative detection system and explore the clinical application effect of dust mite extract and component detection. The fluorescent magnetic particle chemiluminescence method was used to verify the analytical performance of sIgE for house dust mite (D1), dust mite (D2) extracts, and their components (Der p 1, Der p 2, Der p 10, and Der p 23), including precision, limit of blank (LoB), limit of detection (LoD), linear range, and interfering factors. This is a retrospective cohort study. A total of 50 patients with allergic rhinitis and 50 patients with allergic asthma diagnosed at Zhongshan Hospital Affiliated to Fudan University from January 2022 to August 2023 were selected, along with 70 apparently healthy individuals who underwent physical examinations in the hospital as the healthy control group. The positive rates of each sIgE component in the three groups were compared, and the receiver operating characteristic (ROC) curve for diagnosing dust mite allergy was plotted. The results showed that the fluorescent magnetic particle chemiluminescence method for detecting sIgE demonstrated good repeatability and intermediate precision within the range of 0.1-100 kU/L. The LoB, LoD, and linear range all met the specified requirements. Except for Der p 10, which was interfered by the presence of conjugated bilirubin and free bilirubin (exceeding 40 mg/dl), the detection of other allergens was not significantly affected by common endogenous substances. In healthy individuals, 10% had positive sIgE for dustmite extract; in asthmatic and allergic rhinitis patients, the positive rates were 70% and 82%, respectively. The double positive rate of D1 and D2 in the healthy group was 8.6%, while in asthmatic and allergic rhinitis patients, it was 66% and 70%, respectively. When 0.35 kU/L was used as the threshold, the sensitivity of sIgE for dust mite extract to predict component positivity was 100%, specificity was 61.5%, positive predictive value (PPV) was 80.2%, and negative predictive value (NPV) was 100%. When the threshold was optimized to 0.78 kU/L, the sensitivity was 96.8%, specificity was 92.1%, PPV was 95.2%, and NPV was 94.6%. In conclusion, the repeatability, intermediate precision, LoB, LoD, linear range, and anti-interference ability of the fluorescent magnetic particle chemiluminescence method for detecting sIgE meet the requirements of laboratory quality management. This ensures detection quality, meets clinical needs, and can be used for the auxiliary diagnosis of allergic diseases.

Objective:To establish and optimize an autoverification system for thyroid function test reports of 5 items using historical test data.Methods:Based on the docoment' Autoverification of Clinical Laboratory Quantitative Test Results′, CLSI AUTO 10-A and AUTO 15 guidelines, an autoverification system for thyroid function test reports of 5 items was established combining with manual verification experience. A total of 193 860 thyroid function test reports of 5 items in 2021 were collected for the assessment of the original system. Totally 210 097 thyroid function test reports of 5 items in 2022 and 299 198 reports in 2023 were collected for the optimization of the autoverification system. There were 160 666 thyroid function test reports of 5 items from the first half of 2024 for the manual and autoverification comparison after optimization.Results:The pass rate of the autoverification system based on original thyroid function report in 2021 was 69.56%(134 849/193 860). The optimized system utilizing historical data from 2022 and 2023 covered 21 pattern rules and established verification for different patterns including range rules, delta check rules, and review rules. Taking manual verification as the standard for the data from the first half of 2024, the sensitivity and specificity of the optimized system were 100% (499/499) and 81.57% (130 646/160 167), respectively, with a false-negative rate of 0. The concordance rate between autoverification and manual verification was 81.63% (131 145/160 666), and the pass rate was 81.32% (130 646/160 666).Conclusion:Establishing and optimizing the autoverification system for thyroid function tests of 5 items using historical test data, and formulating verification rules for different patterns can be applied to clinical practise, which not only ensures the accuracy of test reports but also improves work efficiency, allowing continuously optimized and perfected of the system.

The patient is a 60 year old male who has been experiencing thrombocytosis for over 2 years. He was treated outside the hospital in August 2023 due to acute myocardial infarction. After he left the hospital, there was still dizziness and persistent elevation of hemoglobin and platelets during follow-up. In November 2023, the patient went to Zhongshan Hospital affiliated with Fudan University for treatment. After admission, elevated platelets and hemoglobin were found, and genetic testing showed positive mutations in JAK2-V617F and CALR gene L367fs * 46, diagnosed as chronic myeloproliferative neoplasms (polycythemia vera and primary thrombocythemia). Discharge order was 0.1 g of hydroxyurea once a day. Follow up after six months showed improvement in hemoglobin and platelets compared with that at admission. This case suggests that classic driver gene mutation testing of myeloproliferative neoplasm is an important indicator for disease diagnosis for patients with thrombocytosis and hemoglobin increase.

The concept of precision oncology and the development of novel anti-cancer drugs have driven the progress of tumor molecular diagnosis. Breakthroughs in new technologies, such as next-generation sequencing and liquid biopsy, have opened a new page for tumor molecular diagnosis. The clinical applications of molecular diagnosis have completely covered the whole process of tumor diagnosis and treatment. However, the clinical implementation of these new technologies clinically still face to challenges. In the future, the field of tumor molecular diagnosis will focus more on the rational and compliant application of new technologies, as well as taking full advantages of artificial intelligence and decision support tools, to elevate clinical application value of molecular diagnosis, and consequently to drive further development of precision oncology.

Objective:To evaluate the diagnostic performance of the 0-2 h high-sensitivity cardiac troponin T (hs-cTnT) cutoff recommended by the guidelines for the rule-out and rule-in diagnosis of suspected non-ST-segment elevation myocardial infarction (NSTEMI) patients of different age groups.Methods:This is a retrospective cohort study. Clinical data of 4 050 suspected NSTEMI patients who visited the Chest Pain Center of Zhongshan Hospital affiliated with Fudan University from January 2020 to December 2021 were retrospectively analyzed. Patients who visited from January 2020 to April 2021 (2 650 patients) were included as derivation cohort, and those who visited from May to December 2021 (1 400 patients) were included as validation cohort. The diagnostic performance of the guideline-recommended hs-cTnT 0-2 h cutoff for the rule-out and rule-in of NSTEMI diagnosis was compared among subgroups of patients aged ≤60, >60-70, and >70 years in the derivation group. Rule-out sensitivity, negative predictive value, and rule-out proportion, rule-in specificity, positive predictive value, and rule-in proportion were assessed. Cutoffs were established for subgroups with relatively lower diagnostic performance and validated in the validation group. Major adverse cardiovascular events (MACE) within 30 days after patient visit were used as the outcome, and survival curves were plotted using Kaplan-Meier curves, log-rank tests were used to analyze the incidence of MACE.Results:The sensitivity for ruled-out NSTEMI using the guideline-recommended 0-2 h cutoff in the subgroups of patients aged ≤60, >60-70, and >70 years in the derivation group was 100%; the negative predictive value was 100%; the ruled-out rates were 47.6% (331/696), 45.9% (491/1 070), and 28.5% (252/884), respectively. The specificity for ruled-in NSTEMI was 88.3%, 90.9%, and 86.4%, respectively; the positive predictive values were 55.3%, 59.3%, and 58.2%, respectively; the ruled-in rates were 22.6% (157/696), 19.5% (209/1 070), and 27.0% (239/884), respectively. With a requirement of sensitivity and negative predictive value >99%, the ruled-out cutoff for the subgroup of patients aged >70 years in the derivation group was established as 0 h hs-cTnT <6 ng/L or 0 h hs-cTnT<22 ng/L and 0-2 h Δhs-cTnT <5 ng/L, which increased the ruled-out rate of the subgroup aged >70 years to 45.6% (403/884). In the validation group, 42.2% (196/465) patients could be ruled-out. The incidence of MACE within 30 days for ruled-out patients aged >70 years using the established cutoff was 0.Conclusion:The diagnostic performance for the ruled-out and ruled-in diagnosis using the guideline-recommended 0-2 h hs-cTnT cutoff are relatively consistent across different age groups, but the ruled-out rate for patients aged >70 years is lower than for those aged ≤60 and >60-70 years. The ruled-out cutoff established in this study can be used to improve diagnostic performance of thus indicator on suspected NSTEMI patients.

Objective:To analyze the variation trends in the levels of apolipoprotein B (ApoB), the ratio of apolipoprotein B to low-density lipoprotein cholesterol (ApoB/LDL-C), and non-high density lipoprotein cholesterol (non-HDL-C) among patients and individuals undergoing physical examinations at Zhongshan Hospital, Fudan University from 2014 to 2024.Methods:Data on ApoB, LDL-C, and nonHDL-C levels were collected from individuals (the overall population) who visited or underwent physical examinations at our hospital from January 1, 2014 to December 31, 2024, as well as from individuals (the fixed population) who were tested annually over the 11-year period. The Mann-Kendall test combined with Sen slope estimation was used to analyze the trends. The abnormal rates of ApoB and non-HDL-C in both the overall and fixed populations, as well as the changes in the first and last test results over the 11 years in the fixed population, were also analyzed.Results:The overall population totaled 1 679 440 cases, aged 57 (45, 67) years, and 718 738 cases (42.8%) were female, of which 1 250 234 cases (74.4%) were in the patient population and 429 206 cases (25.6%) were in the health check population. The fixed population of 1 560 cases was 56 (45, 65) years old and 655 cases (42.0%) were female, of which 1 044 cases (66.9%) were in the patient population and 516 cases (33.1%) in the health check population. Between 2014 and 2024, the overall population ApoB decreased from 0.842 g/L to 0.822 g/L (Sen slope -0.001 g·L -1·year -1, P=0.01), the abnormality rate decreased from 24.70% to 22.03% (Sen slope -0.50%/year, P=0.06), and 69.4% of the fixed population showed no change in the subgroups of initial and final tests. ApoB/LDL-C increased from 0.824 to 0.868 (Sen slope -0.003/year, P=0.72). Non-HDL-C decreased from 3.46 mmol/L to 3.32 mmol/L (Sen slope 0.018 mmol·L -1·year -1, P=0.35), with a statistically significant upward trend since 2019 (Sen slope 0.037 mmol·L -1·year -1, P=0.008), and the anomaly rate decreased from 24.3% to 22.7% (Sen slope 0.55%/year, P=0.64), with a statistically significant upward trend since 2019 (Sen slope 1.53%/year, P=0.014), and no change in the grouping of the first and last tests in 75.0% of the fixed population. The trends in the above items were consistent between the overall population and the fixed population. 20-<40 year olds had the most significant upward trend in non-HDL-C along with the least significant downward trend in ApoB/LDL-C and ApoB. Conclusion:ApoB in the overall and fixed populations from 2014-2024 in a Shanghai hospital showed a decreasing trend, and non-HDL-C and abnormality rates showed an increasing trend from 2019 onwards.

Objective:To analyze the trend of lipid changes in patients and individuals undergoing physical examination at Zhongshan Hospital of Fudan University from 2014 to 2024, providing evidence for the formulation of cardiovascular disease prevention and control strategies.Methods:A total of 2 657 835 individuals (general population) who underwent lipid testing during medical visits or physical examinations at Zhongshan Hospital of Fudan University from January 1, 2014, to December 31, 2024, were selected. Among them, 6 234 individuals who were tested consecutively for 11 years were considered as the fixed population. Lipid levels were analyzed across different genders and age groups. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were analyzed. The trends in lipid changes and the abnormal rates of TC (≥5.18 mmol/L) and LDL-C (≥3.40 mmol/L) in both the general and fixed populations were statistically analyzed.Results:The median age of the general population was 53 (41, 63) years, with 1 498 533 males (56.4%); 1 149 662 individuals (43.3%) were from the physical examination group. The median age of the fixed population was 52 (39, 62) years, with 3 262 males (52.3%); 2 955 individuals (47.4%) were from the physical examination group. Over an 11-year period, the logarithmically transformed TG (lnTG) in the general population slightly increased from 1.35 mmol/L to 1.36 mmol/L (Sen slope=0.007 mmol·L -1·year -1; S=27, P=0.043). Although there were fluctuations in TC, LDL-C, and HDL-C, the trends were not statistically significant ( P>0.05). However, in the subset of the population undergoing regular health check-ups, TC showed a steady increase over time ( S=27, P=0.043). Within a fixed population over the same 11-year period, there were no statistically significant changes in lipid profiles ( P>0.05). Nevertheless, in the fixed subset undergoing regular health check-ups, both TC and lnTG exhibited an upward trend (TC: S=27, P=0.043; lnTG: S=31, P=0.020), while in the fixed subset seeking medical attention, TC and LDL-C demonstrated a downward trend (TC: S=-31, P=0.020; LDL-C: S=-27, P=0.043). Trends in lipid profiles varied among different genders and age groups. Specifically, both men and women aged 20-<40 years old showed an increase in TC, abnormal TC rates, and abnormal LDL-C rates ( P<0.05). Conversely, in the fixed population, women over 60 years old exhibited a decrease in TC, abnormal TC rates, and abnormal LDL-C rates ( P<0.05). Conclusion:During the period from 2014 to 2024, there were slight fluctuations in the average lipid levels of both the general and fixed populations. Notably, TC, abnormal TC rates, and abnormal LDL-C rates increased among men and women aged 20-<40 years old, while these parameters decreased among women over 60 years old in the fixed population.

Objective:To compare the differences in specimen results between the intelligent robotic phlebotomy group and the manual venipuncture group, and to evaluate the clinical applicability of the autonomous blood collection system.Methods:From January 20 to October 28, 2022, 154 volunteers at Zhongshan Hospital, Fudan University underwent paired blood collections (robotic and manual) within 5 minutes. The collected samples were analyzed for: hemolysis index (HI), alanine transaminase (ALT), aspartate transaminase (AST), L-γ-glutamyltransferase (γ-GT), lactate dehydrogenase (LDH), urea nitrogen (UREA), creatinine (CRE), uric acid (UA), glucose (GLU), total cholesterol (TC), triglyceride (TG), natrium (Na), kalium (K), chlorine (Cl), creatine kinase (CK), CK-MB, CK-MM, and neuron-specific enolase (NSE). Statistical analyses used t-tests and Wilcoxon signed-rank tests.Results:The results of two different blood collection methods revealed that the HI values of 154 specimens in the intelligent robot blood collection group were all less than 20SI, while 7 specimens (4.54%) in the manual blood collection group had HI values exceeding 20SI; In the comparison of 17 biochemical and immunological markers, there were statistically significant differences between groups in 8 items including γ-GT[20.00(15.00, 37.75)U/L vs. 19.00 (14.00, 36.25)U/L, Z=2.497, P<0.05], LDH[165.5 (147.0, 183.0)U/L vs. 173.0 (155.0, 193.0)U/L, Z=8.629, P<0.05], TC[(5.002±0.856)mmol/L vs.(5.031±0.870) mmol/L, t=-3.006, P<0.05], K[4.1 (4.0, 4.3)mmol/L vs. 4.3 (4.1, 4.4)mmol/L, Z=5.592, P<0.05], CK[97.00 (73.00, 133.00)U/L vs. 99.00 (74.75, 136.25)U/L, Z=3.490, P<0.05], CK-MB[13 (11, 15)U/L vs. 14 (12, 16)U/L, Z=6.581, P<0.05], CK-MM[84.00 (60.00, 119.00)U/L vs. 83.50 (58.75, 118.00)U/L, Z=3.790, P<0.05], and NSE[10.600 (9.500, 11.700)ng/ml vs. 11.950 (10.475, 13.725)ng/ml, Z=8.151, P<0.05]. Conclusions:In the collection of serum samples, intelligent blood collection robots can achieve standardization and normalization of specimen collection volume and mixing in the pre-analysis stage. The hemolysis related indicators of the collected specimens are lower than those of the manual collection group, and can be used for the collection of clinical serological specimens.

Objective:To explore the impact of Epstein-Barr Virus(EBV) infection on treatment response and survival in newly diagnosed multiple myeloma(MM).Methods:The clinical data of 196 patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from June 1st, 2019 to February 25th,2021 were analyzed retrospectively and divided into EBV-positive group (106 cases) and negative group (90 cases) according to the primary EBV DNA results in peripheral blood mononuclear cells.To analyse the distribution of EBV positive rates in each type and in each stage of the Revised International Staging System (R-ISS), and to compare EBV DNA loads in EBV-positive patients among R-ISS stages.Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis between the two groups.The clinical prognosis of EBV-positive patients was summarized through survival analysis and Cox regression.Results:The EBV positive rate in patients with newly diagnosed MM was 54% (106/196), with the highest rate in patients with κ light chain type (9/12).Patients with R-ISS stage Ⅲ had a significantly higher positive rate than with stage Ⅰ ( χ2=4.68, P=0.031) and stage Ⅱ ( χ2=6.04, P=0.014), but there was no significant difference in EBV DNA loads between EBV-positive MM patients by stage ( Z=3.27, P=0.195).Serum creatinine (Scr) and β 2-microglobulin (β 2-MG) levels were higher in the EBV-positive group than in the EBV-negative group ( Z=1.98, P=0.048 and Z=2.08, P=0.038), and the occurrence of t(4;14) was also higher in the EBV-positive group ( χ2=3.93, P=0.047).The proportion of complete response (CR)/stringent complete response(sCR) and very good partial response(VGPR) after completion of the fourth chemotherapy were significantly lower in the EBV-positive group than in the EBV-negative group ( χ2=12.82, P=0.001 and χ2=8.30, P=0.004), and a higher rate of progressive disease (PD) occurred in the EBV-positive group ( χ2=4.48, P=0.046).The 2-year progression-free survival (PFS) of MM patients was shorter in the EBV-positive group compared to that in the EBV-negative group ( Z=-4.50, P0.01).Cox regression analysis showed that R-ISS stage Ⅲ ( HR=5.38, 95% CI 1.28-22.56, P=0.021), failure to achieve VGPR after the fourth chemotherapy ( HR=3.02, 95% CI 1.42-6.46, P=0.004), EBV-positive ( HR=1.98, 95% CI 1.02-3.87, P=0.045), with 1q21 amplification ( HR=2.35, 95% CI 1.16-4.75, P=0.017) and 13q14 deletion ( HR=1.93, 95% CI 1.01-3.67, P=0.046) were independent risk factors for PFS in newly diagnosed MM. Conclusions:EBV infection is an independent risk factor for poor prognosis, which has important clinical implications for the outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.