Objective To explore the use of indirect methods to establish a reference interval for serum car-bohydrate antigen 242(CA242)in adults in Shanghai and to validate it.Methods A total of 51 897 cases of CA242 testing data from the laboratory information management system of the Department of Clinical Labo-ratory at the hospital from August 2022 to July 2023 were collected.After data cleaning and normal transfor-mation,the Turkey method was used to remove outliers,and 19 653 cases of data were finally included in the study.Then,the Hoffmann method was used to establish the P95 reference interval for serum CA242.The study selected 691 apparently healthy individuals from January to March 2024 to validate the self built refer-ence interval for CA242.The physical examination population with the reference interval recommended by the reagent instructions≤CA242 value

Objective:To compare the distribution differences of serum protein electrophoresis (SPE) among different gender and age individuals, and to explore the clinical application of SPE screening monoclonal gammopathy.Methods:A retrospective analysis was conducted based on the SPE results obtained from 533 989 cases enrolled from January 2018 to December 2019 at Zhongshan Hospital Affiliated to Fudan University. Among these patients, 435 479 inpatients were from departments of hematology, nephrology, spinal surgery, endocrinology, and rheumatology and immunology; and 98 510 were apparently healthy individuals. The distributions of albumin, α1 globulin, α2 globulin, β1 globulin, β2 globulin and γ globulin in different gender and age groups (≤20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, ≥91 years old) were compared. A total of 10 014 cases were selected by immunofixation electrophoresis (IFE). The positive detection rates of different SPE bands and IFE bands were analyzed. The sensitivity and specificity of SPE methods were determined according to IFE results as the gold standard.Results:No significant difference was examined in the proportion of SPE bands between different genders ( P>0.05). There were statistically significant differences in the proportion of albumin bands between apparently healthy individuals and hospitalized patients at different ages (apparently healthy individuals: F=5.12, P<0.05, inpatients: F=4.18, P<0.05), and all of them decreased with the increase of age. The proportion of γ globulin bands increased with age (apparently healthy individuals: F=1.34, P<0.05; inpatients: F=1.24, P<0.05). The sensitivity of SPE was 69% (2 098/3 051), and the specificity was 97% (6 721/6 963). Compared with IFE method, the positive detection rate of monoclonal gammopathy was significantly different (χ2=5 049.94, P<0.05). The positive rate of monoclonal gammopathy in γ globulin region (21.11%, 2 114/10 014) was higher than that in β globulin region (3.28%, 328/10 014) (χ2=90.74, P<0.05) and β-γ globulin region (1.63%, 163/10 014) (χ2=44.34, P<0.05). IgG and IgM bands are common in γ globulin region. Among them, IgG-κ type accounted for 94.1% (995/1 058), IgG-λ type accounted for 94.8% (690/728), IgM-κ type accounted for 89.2% (222/249), IgM-λ accounted for 83.8% (62/74). IgA bands are common in β region, of which IgA-κ accounted for 49.8% (103/207) and IgA-λ accounted for 51.6% (149/289). The positive rate of monoclonal gammopathy of IgG-κ type was the highest (10.57%, 1 058/10 014), and the positive rate of monoclonal gammopathy of IgM-λ type was the lowest (0.74%, 74/10 014). Conclusions:With increasing age, the proportion of albumin band in SPE decreased and the proportion of γ globulin band increased. IgG and IgM type monoclonal gammopathy is mostly found in the gamma region, with a higher detection rate in IgG type. IgA type monoclonal gammopathy is mostly found in the β region, with a lower detection rate.

Objective:To investigate the characteristics and distribution of monoclonal gammopathy in clinical patients.Methods:A total of 936 171 patients (508 449 males and 427 722 females) who received capillary zone electrophoresis in Zhongshan Hospital Affiliated to Fudan University from January 2012 to December 2021 were selected, from which 14 945 patients with abnormal bands were screened as the study subjects, including 10 173 males and 4 772 females and the age 21-102 (65±13) years old. According to the age, patients were divided into 8 groups: 21-30 years old (168 cases), 31-40 years old (405 cases), 41-50 years old (1 326 cases), 51-60 years old (3 068 cases), 61-70 years old (4 985 cases), 71-80 years old (3 288 cases), 81-90 years old (1 519 cases), and≥91 years old (186 cases). The diagnostic results of the 14 945 patients with abnormal bands were collected and were divided into tumor group (5 196 cases) and non-tumor disease group (9 749 cases) according to the presence of tumor. The distribution of abnormal bands in different gender, age, and disease groups were retrospectively analyzed. Among the 14 945 patients, 4 988 cases underwent immunofixation electrophoresis, excluding 336 negative cases and 412 cases of double clonal bands reaction, and 4 240 patients with monoclonal immunoglobulin (M protein) reaction were selected as the study subjects, including 2 794 males and 1 446 females aged 21-102 (67±12) years old. They were divided into 8 groups according to the age: 21-30 years old (18 cases), 31-40 years old (91 cases), 41-50 years old (364 cases), 51-60 years old (862 cases), 61-70 years old (1 455 cases), 71-80 years old (904 cases), 81-90 years old (486 cases), and≥91 years old (60 cases). The diagnostic results and immunoglobin subtypes (IgA-κ, IgA-λ, IgG-κ, IgG-λ, IgM-κ, IgM-λ, κ, λ) of patients were collected, and the distribution of monoclonal gammopathy in different gender, age and disease groups were retrospectively analyzed.Results:Among 936 171 patients, 14 945 cases showed abnormal bands in electropherograms with a detection rate of 1.60%; the detection rates of abnormal bands in males and females were 2.00% (10 173/508 449) and 1.12% (4 772/427 722), respectively, with a statistically significant difference ( P<0.01). There was a significant difference in the detection rate of abnormal bands among different age groups ( P<0.01); among them, the highest detection rate of abnormal band in group of ≥91 years old was 5.98%, and the ratio of male to female was 1.67∶1. Among the 14 945 cases of abnormal bands, patients aged 51-60, 61-70 and 71-80 accounted for 20.53% (3 068 cases), 33.36% (4 985 cases) and 22.00% (3 288 cases), respectively, and the differences among the age groups were statistically significant (χ 2=115.82, P<0.01). In the tumor group, the top 3 tumors with abnormal bands were plasmacytoma with 1 123 cases, lymphoma with 289 cases, and leukemia with 49 cases. The detection rate of abnormal bands in electropherograms of plasmacytoma was 89.92% (1 123/1 249), which was higher than that in lymphoma and leukemia [6.73% (289/4 296) and 6.40% (49/766), respectively, P<0.01]. Among 4 240 patients with positive M protein, the proportion of 51-60, 61-70 and 71-80 years old patients were 20.33% (862/4 240), 34.32% (1 455/4 240) and 21.32% (904/4 240), respectively, and the differences among age groups were statistically significant ( P<0.01). The results of M protein types showed that the proportion of IgG-κ type was the highest in both genders, with 32.28% (902/2 794) in males and 34.30% (496/1 446) in females. In the 21-30, 31-40, and 41-50 age groups, the proportion of IgG-λ was the highest, which were 38.89% (7/18), 36.26% (33/91) and 34.07% (124/364) in these groups respectively. However, the proportions of IgG-κ were the highest in either of the 51-60, 61-70, 71-80, 81-90 and ≥91 years old groups, which were 33.87% (292/862), 34.16% (497/1 455), 31.53% (285/904), 34.57% (168/486), 28.33% (17/60), respectively, and the differences among all age groups and gender groups had statistical significance ( P<0.01). Among patients with positive M protein in the tumor group, plasmacytoma accounted for 14.22% (603/4 240), followed by lymphoma 6.30% (267/4 240); among non-tumor diseases, M proteinemia accounted for the highest proportion (7.24%, 307/4 240), followed by pulmonary infection (5.47%, 232/4 240). Conclusions:The detection rate of abnormal bands in capillary zone electrophoresis may increase with age, and is higher in males than in females in the same age group; different malignant tumor diseases can also show abnormal bands in capillary zone electrophoresis, but they are still mainly hematological tumors. Among the positive results of M protein, 61-70 years old group accounts for the highest proportion; the most common type of monoclonal gammopathy is IgG type; in the age group of 21-50 years, the proportion of IgG-λ type is the highest; in the group of >50 years old, the proportion of IgG-κ type is the highest; in the diagnosis of positive monoclonal gammopathy, the top 3 diseases are all hematological diseases, including plasmacytoma, monoclonal gammopathies and lymphoma.

Objective:To retrospectively compare the clinical effects of the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the European Kidney Function Consortium (EKFC) equation based on creatinine to estimate glomerular filtration rate (eGFRcr) in a Chinese population.Methods:Patients and healthy individuals who visited the Zhongshan Hospital, Fudan University, between January 1, 2023, and December 31, 2023, were enrolled. The exclusion criteria were age<18 years, amputees, pregnant women, patients with muscle-related diseases, and patients who had undergone ultrafiltration or dialysis. The final study population included 660 078 individuals with a median age of 58 years (44, 68), 56.51% (372 987/660 078) of them were men. eGFRcr was calculated using the 2021 CKD-EPI, EKFC equations and initial 2009 CKD-EPI equation. Results were compared by differences (P 10), charges in population distribution and impact on staging of chronic kidney disease (CKD) by gender, age and creatinine results. Results:Compared with the results of 2009 and 2021 CKD-EPI eGFRcr, the P 10was 99.99% ( R 2=0.997). When applying the 2021 CKD-EPI eGFRcr equation, there was a slight overestimation of 3.77 (2.92, 4.47) ml/(min×1.73 m 2). 86.42% (570 455/660 078)participants had higher eGFRcr owing to the utilization of the 2021 CKD-EPI equation, which did not cause CKD stage change. A total of 12.35% (81 514/660 078) of subjects had different CKD stage with the higher 2021 CKD-EPI eGFRcr. 1.23% (8 109/660 078) had lower eGFRcr but no change in the CKD stage with the 2021 equation. Compared to the 2009 CKD-EPI eGFRcr results, the EKFC eGFRcr demonstrates P 10 values of 89.79%, with a correlation coefficient of R 2=0.976. The overall eGFRcr values using the EKFC equation were decreased by 4.63(-2.22, -7.04) ml/(min×1.73 m 2). There were 75.14% (495 992/660 078) individuals whose eGFRcr results were lower in EKFC equation, which did not cause CKD stage change. There were 15.63% (103 161/660 078) leading to a different CKD stage. Additionally, 8.80% (58 077/660 078) individuals with a higer eGFRcr result did not change CKD stage, while 0.43% (2 848/660 078) experienced a change in CKD staging due to the overestimation. Conclusions:Compared with the 2009 CKD-EPI eGFRcr results, the 2021 CKD-EPI eGFRcr results were slightly higher and had good consistency in different genders and ages. However, the EKFC eGFRcr was generally lower than 2009 CKD-EPI eGFRcr, showing poor consistency. The differences between eGFR equations should be considered when judging the CKD stage of patients.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To assess the role of Delta-RBC parameters in the automated hematocrit analyzer RET channel for the recognition of cold agglutinins (CA) and to explore the value of RET channel optical method parameters in correcting interference with CA.Methods:This is a retrospective study. The Cas group included 68 samples with Cas interference and the control group included 45 samples without CA interference. All specimens were collected from Zhongshan Hospital Fudan University Outpatient Department from January 2022 to January 2023. Specimens in both the CA and Control group were examined using the CBC+RET channel at room temperature. Recorded and calculated the Impedance method test parameters RBC-I, HGB, HCT-I, MCH-I, MCV-I, MCHC-I and the Optical method test parameters RBC-O, HCT-O, MCH-O, R-MFV, MCHC-O, Delta-RBC. Examined the specimens in the CA group using the CBC channel after prewarmed at 37 ℃ for 2 h, and Impedance method parameters RBC-I 37 ℃ 2 h, HGB 37 ℃ 2 h, HCT-I 37 ℃ 2 h, MCH-I 37 ℃ 2 h, MCV-I 37 ℃ 2 h, MCHC-I 37 ℃ 2 h were recorded. The ROC curves were used to analyze the discrimination efficacy of Delta-RBC in identifying CA interference, and the Bland-Altman method was used to analyze the consistency between the results of the optical method RBC parameters at room temperature and the results of the impedance method after prewarming. The correlation analysis was performed using Pearson and Spearman correlation analysis to analyze the results of the RBC parameters before and after prewarming in the CA group. Result:If Delta-RBC was used as diagnostic indicators for the identification of CA interference, the best cut-off value was 1.065, with AUCs of 0.998. In the CA group, the correlation coefficients between RBC-O, HCT-O, R-MFV, MCH-O, MCHC-O, and RBC-I 37 ℃ 2 h, HCT-I 37 ℃ 2 h, MCV-I 37 ℃ 2 h, MCH-I 37 ℃ 2 h, MCHC-I 37 ℃ 2 h were 0.985, 0.981, 0.729, 0.870, and 0.649, respectively. The percentages within the limits of agreement of the percentage differences between the results of the two methods were 95.6%, 92.6%, 95.6%, 94.1%, and 95.6%, respectively. Conclusions:The RBC parameter Delta-RBC from RET channel optical method can be used as an indicator to effectively assist in the clinical determination of the presence of CA. Reporting results using the optical method RBC parameters of the RET channel can correct the interference of CA without specimen pre-treatment and obtain more correct results of complete blood counts.

Objective:To compare the detection performance of serum free light chain (sFLC) in two platforms and evaluate the comparability of serum free light chain results in patients with multiple myeloma (MM).Methods:To evaluate the detection performance (repeatability, accuracy, linear range, reference range, interfering substances, etc.) of sFLC kit based on polyclonal antibodies. Spearman correlation analysis and Bland-Altman were used to analyze 214 sFLC results obtained on two detection platforms at the same time to evaluate the correlation between the results of the two methods and analyze the causes of methodological bias. 119 cases with aMM and 23 cases of disease control group (AL, WM, POEMS syndrome, MGUS, diffuse large B-cell lymphoma) initially diagnosed in the hematology department of Zhongshan Hospital of Fudan University from March 2020 to March 2021 were all included. A retrospective analysis was conducted to calculate the area under the curve of receiver operating characteristic (AUC-ROC) and obtain the optimal sensitivity and specificity cut-off points for the diagnosis of MM patients on monoclonal antibody platform.Results:Repeatability, accuracy, linear range, reference interval and anti-interfering capacity of the detection platform based on polyclonal antibodies were verified to meet clinical needs. The overall consistency of FLC/κ, FLC/λ and κ/λ ratios in two methods was 89.3%, 84.1% and 77.1% respectively; but the correlation results were highly heterogeneous. The correlation coefficient of FLC/κ R 2 was 0.922( P<0.001), while the correlation coefficients R 2of the FLC/λ and κ/λ ratios were only 0.349 and 0.441( P<0.001). After segment analysis, it was found that the correlation of FLC/λ was improved within the linear range and R 2 could rise to 0.78( P<0.001). Compared with monoclonal antibody platform, the vast majority points of FLC/κ fell within the 95% limit by Bland Altman analysis. While the results of FLC/λ on polyclonal antibody platform showed significant positive bias. The AUC of MM diagnosis on monoclonal antibody platform was 0.751 ( P=0.001), and the optimal cutoff value was 24.67. Conclusion:The overall consistency between the two platforms was good, but there were significant differences between the results, so they were not comparable and could not be interchanged. For monitoring the prognosis of patients with multiple myeloma, the same platform should be selected for testing.

We report a case of a 44-year-old female patient with acute liver failure and hepatic encephalopathy. The patient received artificial liver treatment and underwent allogeneic orthotopic liver transplantation at 14 days after admission. Laboratory examination reported a small number of green cytoplasmic inclusions in neutrophils on the peripheral blood smear at 68 days after admission. The patient eventually died of liver failure at 71 days after admission. Green inclusions are bright green or blue-green inclusions presented in the cytoplasm of neutrophils in Wright-Giemsa stained peripheral blood smears, and is associated with liver failure and high short-term mortality.

Objective : To investigate whether the application of melatonin (MT) in embryo culture in vitro can improve the treatment effect of in vitro fertilization embryo transfer(IVF⁃ET) in patients with decreasing ovarian reserve (DOR) . Methods : 128 DOR patients receiving assisted reproductive therapy were collected. All patients were treated with an antagonist scheme of super⁃ovulation. Patients were divided into melatonin group (n = 56) and control group (n = 72) according to whether melatonin ( melatonin concentration 10 - 9 mol/L) was added into embryo culture medium. Results : There was no statistically significant difference in oocytes fertilization rate and cleavage rate between the two groups during later embryo culture , but blastocyst formation rate ( 65. 22% vs 56. 16% ) and high⁃quality blastocyst rate (52. 96% vs 40. 94% ) in the melatonin group were higher than those in the control group , and the differences were statistically significant ( P < 0. 05 ) . There were no significant differences in the implantation rate (50. 00% vs 38. 67% ) and clinical pregnancy rate (48. 39% vs 46. 00% ) of blastocysts after freezing⁃thawing between the two groups , but the cycle number of high⁃quality blastocysts obtained in the melatonin group was higher than that in the control group (85. 71% vs 69. 44% ) , and the difference was statistically significant (P < 0. 05) . Conclusion In a way , the application of melatonin in the in vitro culture of early embryos can promote the development of oocytes in patients with DOR , improve the quality of embryos , and finally substantially improve the therapeutic effect of such patients.