Fudan University Research Articles

[Analysis of efficacy and prognosis of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors. Methods: In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children's Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors. Results: Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis (HR=2.55, 95%CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant (HR=2.96, 95%CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions: Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

Impact of immune checkpoint inhibitors (ICIs) therapy on interferon-γ release assay (IGRA) and diagnostic value in non-small cell lung cancer (NSCLC) patients

BackgroundTuberculosis (TB), a highly contagious respiratory disease, presents a significant global health threat, with a notable increase in incidence reported by the WHO in 2022. Particularly, the interplay between TB and non-small cell lung cancer (NSCLC) gains attention, especially considering the rising use of immune checkpoint inhibitors (ICIs) in cancer treatment. This interplay may influence TB diagnostics and reactivation, warranting a closer examination.MethodsA retrospective analysis was conducted on clinical data of NSCLC patients with positive T-SPOT results before undergoing anti-tumor treatment at Zhongshan Hospital (Xiamen), Fudan University, from January 1, 2021 to December 31, 2022. We assessed the incidence of tuberculosis reactivation and treatment outcomes among these patients. Moreover, we compared the differences in tuberculosis activity between the ICIs and non-ICIs treatment groups. Additionally, we observed the changes in T-SPOT spot count before and after immunotherapy, analyzing their association with tuberculosis activity and prognosis.ResultsA total of 40 NSCLC patients with positive T-SPOT results before treatment were included in the study, with 26 patients in the ICIs treatment group and 14 patients in the non-ICIs treatment group. The study found no significant differences between the two groups in terms of gender, age, stage, histological type, performance status, driver gene expression, and distant metastasis. With a median follow-up time of 10.0 (6.0-14.5) months, three cases (11.5%) in the ICIs treatment group developed tuberculosis activity, diagnosed at 2, 3, and 12 months after ICIs treatment initiation. Conversely, no tuberculosis activity was observed in the non-ICIs treatment group, and the difference between the two groups was not significant (P = 0.186). Among the 32 patients who received ICIs treatment, spot count dynamics were diverse: four cases (12.5%) showed an increase, 12 cases (37.5%) had no change, and 16 cases (50.0%) had a decrease. During the follow-up, the progression rate (PD) was 50.0%, 75.0%, and 62.5% in the three groups, respectively (P = 0.527). Similarly, the mortality rate was 0%, 25.0%, and 25.0%, respectively (P = 0.106). Interestingly, among the patients with decreased spot counts, three cases (18.75%) were diagnosed with active pulmonary tuberculosis.ConclusionsFor NSCLC patients with a positive T-SPOT response undergoing ICIs treatment, our study observed indications of active tuberculosis. The varied T-SPOT spot count changes post-ICIs treatment suggest a complex interaction, potentially linking T-SPOT spot count reduction to tuberculosis reactivation risk. These preliminary findings underscore the importance of further research to more accurately assess T-SPOT’s diagnostic utility in this context.

Lineage Replacement and Genetic Changes of Four HR-HPV Types during the Period of Vaccine Coverage: A Six-Year Retrospective Study in Eastern China

Objective: This study aimed to provide clinical evidence for lineage replacement and genetic changes of High-Risk Human Papillomavirus (HR-HPV) during the period of vaccine coverage and characterize those changes in eastern China. Methods: This study consisted of two stages. A total of 90,583 patients visiting the Obstetrics and Gynecology Hospital of Fudan University from March 2018 to March 2022 were included in the HPV typing analysis. Another 1076 patients who tested positive for HPV31, 33, 52, or 58 from November 2020 to August 2023 were further included for HPV sequencing. Vaccination records, especially vaccine types and the third dose administration time, medical history, and cervical cytology samples were collected. Viral DNA sequencing was then conducted, followed by phylogenetic analysis and sequence alignment. Results: The overall proportion of HPV31 and 58 infections increased by 1.23% and 0.51%, respectively, while infection by HPV33 and 52 decreased by 0.42% and 1.43%, respectively, within the four-year vaccination coverage period. The proportion of HPV31 C lineage infections showed a 22.17% increase in the vaccinated group, while that of the HPV58 A2 sublineage showed a 12.96% increase. T267A and T274N in the F-G loop of HPV31 L1 protein, L150F in the D-E loop, and T375N in the H-I loop of HPV58 L1 protein were identified as high-frequency escape-related mutations. Conclusions: Differences in epidemic lineage changes and dominant mutation accumulation may result in a proportional difference in trends of HPV infection. New epidemic lineages and high-frequency escape-related mutations should be noted during the vaccine coverage period, and regional epidemic variants should be considered during the development of next-generation vaccines.

Peripheral lymphocyte count as an indicator of radiotherapy effectiveness in hypopharyngeal squamous cell carcinoma.

To explore the predictive significance of baseline absolute peripheral lymphocyte counts (ALC) in the effectiveness of radiation in hypopharyngeal squamous cell carcinoma (HPSCC) patients. A retrospective study of pathologically confirmed HPSCC patients who had definitive radiationbetween January 2020 and January 2022 at Fudan University Eye and ENT Hospital. The routine blood results of patients were obtained to determine if the baseline ALC was connected with the response to radiation. The receiver operator characteristic (ROC) curve and LASSO-based Cox regression were employed to assess the predictive value of ALC for the efficacy of radiotherapy (RT). RT induced a considerable drop in ALC and the level of ALC did not revert to the baseline values 1 year after radiation. The baseline level of ALC was higher in patients who met complete response after RT. The baseline ALC and monocyte counts demonstrated the predictive value of radiation effectiveness and ALC was an independent predictor. In HPSCC, lymphocytes were sensitive to radiation and reduced significantly during RT. The baseline ALC might be regarded as a predictive indicator of the effectiveness of RT.

[Preliminary observation of wearable balance diagnosis and treatment system in evaluating dynamic and static balance function in patients with vestibular vertigo].

A newly developed wearable balance diagnosis and treatment system was studied to evaluate the indexes of the abnormal balance function in patients with vestibular vertigo. A cross-sectional study was carried out. A total of 30 patients diagnosed with non-acute vestibular vertigo in the outpatient department of Eye, Ear, Nose and Throat Hospital Affiliated to Fudan University from July 2022 to May 2023 were selected as the vertigo group, including 13 males and 17 females, and aged (45.7±13.9) years. Meanwhile, 20 healthy controls (8 males and 12 females) were included as the control group, with a mean age of (43.6±8.0) years. The static balance and limits of stability (LOS) function of all subjects were assessed with wearable balance diagnosis and treatment system developed under the leadership of Eye & ENT Hospital of Fudan University. In the static balance test, the ratio of eyes open with cushions to eyes open without cushions in the vertigo group was less than that of the control group[1.20% (0.92%, 1.53%) vs 1.49% (1.22%, 1.81%), P=0.008], indicating that patients with non-acute vestibular vertigo may compensate static balance ability earlier. In vertigo group, the directional control in 8 directions, the maximum excursion in anterior, posterior, right anterior and right posterior directions, the endpoint excursion in the posterior, right posterior, and left posterior directions were all smaller than those of the control group (all P<0.05). The reaction time in the left posterior direction of vertigo group was longer than that of the control group (all P<0.05). Those results indicated that the directional control, maximum excursion and endpoint excursion of LOS could be considered as important reference indexes for dynamic balance function.

[Comparison of efficacy between short-term personalized vestibular rehabilitation supervised by special personnel and fixed vestibular rehabilitation on recurrent peripheral vertigo].

Objective: To explore the efficacy of short-term personalized vestibular rehabilitation supervised by special personnel (ST-PVR) versus fixed vestibular rehabilitation (FVR) on decompensated recurrent peripheral vertigo. Methods: A randomized controlled trial was carried out. Patients diagnosed with decompensated recurrent vertigo in the clinic of Eye & ENT Hospital, Fudan University from January to December 2018 were randomly allocated into FVR and ST-PVR groups via computer-generated randomization. The FVR group received fixed scheme involving gaze stabilization exercises, habituation exercises, balance and gait training, while the ST-PVR group received individualized training programs based on symptoms and vestibular function examination results, with adjustments made according to the progress of recovery. Patient symptoms and vestibular function improvement were assessed using the dizziness handicap inventory (DHI), activities-specific balance confidence (ABC), self-rating anxiety scale (SAS), caloric test, and sensory organization test (SOT) at 2, 4, and 8 weeks of treatment. Results: A total of 44 patients were included, including 16 males and 28 females, with an average age of (50.6±13.5) years. There were 21 cases in the FVR group and 23 cases in the ST-PVR group. In the ST-PVR group, DHI score (49.5±26.8 vs 61.3±21.4, P=0.046) and SAS score (39.1±7.8 vs 44.3±6.6, P=0.021) significantly improved after 2 weeks of treatment, while significant improvement occurred only after 8 weeks of treatment in the FVR group (DHI score: 28.1±15.9 vs 53.1±18.5, P=0.001; SAS score: 35.3±6.7 vs 43.1±8.4, P=0.010). There was no significant change of ABC score in the FVR group after 8 weeks of treatment (86.5±12.9 vs 83.4±18.1, P=0.373), while a significant improvement was observed in the ST-PVR group after 4 weeks of treatment (83.6±15.2 vs 78.4±15.1, P=0.015). The caloric test results showed that after 8 weeks of treatment, the proportion of patients with unilateral weakness<25% increased in both groups [FVR group: 57.1% (12/21) vs 9.5% (2/21), P=0.001; ST-PVR group: 52.2% (12/23) vs 17.4% (4/23), P=0.014]. In the ST-PVR group, the proportion of patients with dominant preference≤25% significantly increased [91.3% (21/23) vs 60.9% (14/23), P=0.016], while there was no significant change in the FVR group [61.9 (13/21) vs 57.1% (12/21), P=0.500]. The proportion of patients with SOT score≥70 in the ST-PVR group increased significantly after 2 weeks of treatment [69.6% (16/23) vs 30.4% (7/23), P=0.009], while the FVR group showed a significant increase only after 8 weeks of treatment [81.0% (17/21) vs 42.9% (9/21), P=0.012]. Conclusion: Both FVR and ST-PVR effectively promote vestibular compensation by improving objective vestibular functions and relieving subjective symptoms and anxiety of the patients with decompensation recurrent vertigo, while ST-PVR might shorten the recovery time and increase balance confidence.

Bibliometric and visualized analysis of posterior chamber phakic intraocular lens research between 2003 and 2023

IntroductionMyopia is causing a major public health concern, with its prevalence increasing globally. This study aimed to discuss posterior chamber phakic intraocular lens (pIOL) research publication trends and hotspots over the past 20 years.MethodsBibliometric analysis was performed using the Web Science Core Collection to investigate posterior-chamber pIOL research publication trends. The extracted records were analyzed, and a knowledge map was built using VOSviewer v.1.6.20. The analysis included visualizing the annual publication count, countries/regions distribution, international and institutional collaborations, author productivity, and journal contribution, in addition to identifying knowledge bases and hotspots. Burst keywords were extracted using CiteSpace v.6.1.R.ResultsIn total, 791 articles on posterior chamber pIOLs published between 2003 and 2023 were retrieved. China had the highest number of publications, whereas Japanese papers received the most citations. Fudan University had the highest number of publications, with articles from Kitasato University having the highest number of citations. Regarding individual research, Xingtao Zhou has published the most significant number of articles, and Shimizu Kimiya had the highest number of citations. The top productive/influential journal was ‘Journal of Cataract &amp;amp; Refractive Surgery’. The top cited references primarily focused on reporting the clinical outcomes of implantable collamer lens (ICL) for individuals with moderate to high myopia. The keywords primarily formed four clusters: posterior chamber pIOL clinical outcomes for myopic astigmatism correction, posterior chamber pIOL implantation complications, ICL size selection and postoperative vault predictions, and postoperative visual quality following posterior chamber pIOL implantation.ConclusionThis study presents the first bibliometric analysis of research trends in posterior chamber pIOL over the past two decades. We investigated the current state and emerging trends of global collaboration and research focal points in this field, offering fresh insights and guidance for researchers.

[Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological analysis of eight cases].

Objective: To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED). Methods: Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed. Results: Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases. Conclusions: CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase Ⅱ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Fudan Zhongshan Plastic Surgery Forum.

The Fudan Zhongshan Plastic Surgery Forum along with the National Continuing Education Course is authorized and supported by the Shanghai Medical Association for Plastic and Reconstructive Surgery and the Fudan University. The annual conference this year along with the course focusing on the "Advances and New Techniques in Plastic Surgery" is successfully held at Zhongshan Hospital affiliated with Fudan University, on August 26-27, 2023 in Shanghai, China.

Microbial Disruptions in Inflammatory Bowel Disease: A Comparative Analysis.

The fecal microbiota was studied in patients with inflammatory bowel disease (IBD), and the characteristics of gut microbiota were compared among patients with different subtypes and stages of IBD, aiming to identify the gut microbiota associated with IBD. Fecal samples were collected from 41 IBD patients (18 patients with ulcerative colitis [UC] and 23 patients with Crohn's disease [CD]) in the Department of Gastroenterology of East China Hospital, Fudan University between January 2021 and January 2022. In addition, fecal samples were collected from 20 healthy volunteers. The fecal microbiota was subjected to 16S rRNA gene sequencing, followed by bioinformatics analysis. There was significant difference in the fecal microbiota between IBD patients and controls. The abundance and diversity of fecal microbiota in the IBD patients were significantly lower than in controls. The relative abundance of Subdoligranulum, Ruminococcus, Anaerostipes and Lachnospira was reduced markedly in the IBD patients. As compared to controls, the relative abundance of Streptococcus increased dramatically in the UC patients. The relative abundance of Lachnoclostridium, Fusobacterium, Cloacibacillus and Erysipelatoclostridium significantly increased in the CD patients. As compared to CD patients, the relative abundance of Alistipes was reduced markedly in the UC patients; the relative abundance of Faecalibacterium, Roseburia and Haemophilus was reduced dramatically in the CD patients. In addition, significant difference was also noted in the fecal microflora between patients with active IBD and those with IBD in remission period. In active IBD patients, the relative abundance of Roseburia, Coprococcus and Ruminiclostridium was reduced significantly. There is intestinal microbiota imbalance in IBD patients, and the abundance of Roseburia, Coprococcus and Ruminiclostridium is reduced significantly in the active period of IBD, which may be related to the active IBD.

Semiquantitative assessment of preganglionic nerves for chronic immune-mediated neuropathies using brachial plexus magnetic resonance imaging.

Brachial plexus magnetic resonance imaging (MRI) is an important noninvasive supplementary diagnostic method of chronic immune peripheral neuropathies, but few MRI studies on the preganglionic nerves have been conducted. This retrospective cross-sectional study aimed to establish a reliable assessment for brachial plexus preganglionic nerve thickness and to use this method to assess and compare nerve characteristics in various types of peripheral neuropathies. Hospitalized patients diagnosed as positive for anti-neurofascin-155 (NF155)-positive autoimmune nodopathy (AN) (NF155+), chronic inflammatory demyelinating polyneuropathy (CIDP), or multifocal motor neuropathy (MMN) at Huashan Hospital of Fudan University in Shanghai, China, who underwent brachial plexus MRI between October 2011 and August 2023 were consecutively recruited for this study. We also recruited participants who underwent brachial plexus MRI during this period with no history of trauma, inflammation, tumors, compression, or degenerative conditions as healthy controls. According to our self-developed semiquantitative assessment of preganglionic nerves, we assessed the bilateral preganglionic C5-C8 nerves individually and scored the enlargement degree from 0 to 4 points. Furthermore, a sum score ≥20 was defined as definite enlargement. A total of 122 participants were enrolled, including 28 with NF155+, 40 with CIDP, 15 with MMN, and 39 healthy controls. In the comparison of the single-nerve scores, we found that there was a significant difference distribution among the four groups (χ2 test; P<0.001), with the patients with NF155+ exhibiting the highest scores in each of the bilateral C5-C8 nerves. In the comparison of the sum scores, a descending tendency was observed in patients NF155+, CIDP, and MMN, with median scores of 11, 4, and 0 points, respectively (Kruskal-Wallis test; P=0.003, P<0.001, and P=0.005, respectively for NF155+ vs. CIDP, NF155+ vs. MMN, and CIDP vs. MMN). The proportion of definite enlargement in those with NF155+ was greater than that in healthy controls (21% vs. 0%; χ2 test; P=0.004), and the sum score at 0 points was lower in the NF155+ group than in CIDP, MMN, and healthy control groups (7% vs. 37%, 87%, and 41%, respectively; χ2 test; P<0.001). This semiquantitative assessment can be a valuable tool for measuring preganglionic nerve enlargement, which was found to be decreased, respectively, in those with NF155+, CIDP, and MMN. Presence of definite enlargement could be a strong indicator of NF155+ in clinic.

Association of Preoperative and Recurrent Serum Carcinoembryonic Antigen and Outcome of Colorectal Cancer Patients with Metastatic Relapse

BackgroundSeldom have the associations of preoperative CEA (p-CEA) and recurrent CEA (r-CEA) levels as well as changes in p-CEA and r-CEA with survival in patients with stage I–III colorectal cancer (CRC) who have experienced metastatic relapse, been thoroughly examined. Methods241 consecutive patients with stage I–III CRC who experienced metastatic relapse at Fudan University Shanghai Cancer Center (FUSCC) between January 2008 and January 2016 were investigated. The influence of p-CEA, r-CEA and CEA alteration on the overall survival (OS) and relapse-to-death survival (RDS) was evaluated. The restricted cubic spline regression model was employed to explore the optimal cut-off value of CEA. ResultsAll 241 patients were categorized into four groups built on their CEA alteration patterns as follows: A, patients presenting elevated p-CEA levels but normal r-CEA levels (P-N); B, patients displaying normal levels of both p-CEA and r-CEA (N-N); C, patients exhibiting elevated levels of both p-CEA and r-CEA (P-P); D, patients with normal p-CEA levels but elevated r-CEA levels (N-P).The correlation between p-CEA and OS (P = 0.3266) and RDS (P = 0.2263) was insignificant. However, r-CEA exhibited a significant association with both OS (P = 0.0005) and RDS (P = 0.0002). Group A demonstrated the longest OS and RDS, whereas group D exhibited the poorest OS and RDS outcomes. For both OS and RDS, the CEA alteration groups served as an independent prognostic indicator. The optimal cut-off threshold for CEA was determined to be 5.1 ng/ml via the restricted cubic spline regression model. Conclusionr-CEA has a stronger correlation with OS and RDS in individuals with stage I–III CRC who have experienced metastatic relapse.The change between p-CEA and r-CEA could further indicate post-relapse survival, thereby facilitating the assessment of mortality risk stratification in stage I-III CRC patients experiencing metastatic relapse.

Effect of vault on predicting postoperative refractive error for posterior chamber phakic intraocular lens based on a machine learning model

Purpose: To investigate how vault and other biometric variations affect postoperative refractive error of implantable collamer lenses (ICLs) by integrating artificial intelligence and modified vergence formula. Setting: Eye and ENT Hospital of Fudan University, Shanghai, China. Design: Artificial intelligence and big data-based prediction model. Methods: 2845 eyes that underwent uneventful spherical ICL or toric ICL implantation and with manifest refraction results 1 month postoperatively were included. 1 eye of each patient was randomly included. Random forest was used to calculate the postoperative sphere, cylinder, and spherical equivalent by inputting variable ocular parameters. The influence of predicted vault and modified Holladay formula on predicting postoperative refractive error was analyzed. Subgroup analysis of ideal vault (0.25 to 0.75 mm) and extreme vault (&lt;0.25 mm or &gt;0.75 mm) was performed. Results: In the test set of both ICLs, all the random forest-based models significantly improved the accuracy of predicting postoperative sphere compared with the Online Calculation &amp; Ordering System calculator (P &lt; .001). For ideal vault, the combination of modified Holladay formula in spherical ICL exhibited highest accuracy (R = 0.606). For extreme vault, the combination of predicted vault in spherical ICL enhanced R values (R = 0.864). The combination of predicted vault and modified Holladay formula was most optimal for toric ICL in all ranges of vault (ideal vault: R = 0.516, extreme vault: R = 0.334). Conclusions: The random forest-based calculator, considering vault and variable ocular parameters, illustrated superiority over the existing calculator on the study datasets. Choosing an appropriate lens size to control the vault within the ideal range was helpful to avoid refractive surprises.

Serum cytokines profile changes in amyotrophic lateral sclerosis

BackgroundAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS. MethodsIn Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL). ResultsThe levels of serum IL-18 were markedly increased in patients with ALS in the first stage (p = 0.016). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50–0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25–175.59] vs 116.44 [102.43–122.19]pg/ml, p < 0.0015). ConclusionIn this study, we identified systemic cytokine profile changes in the serum of ALS patients, especially the elevated IL-18, as well as the decreased IL-21 in elder patients. These changes in serum cytokine profiles may shed new light on an in-depth understanding of the immunopathogenic characteristics of ALS.

Evaluation of AJCC staging system and proposal of a novel stage grouping system in retroperitoneal liposarcoma: the Fudan Zhongshan experience.

Overall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system. The cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell's consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram. A total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate. Compared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop risk-adapted therapy for RPLS patients.

A decrease in integrin α5β1/FAK is associated with increased apoptosis of aortic smooth muscle cells in acute type a aortic dissection

BackgroundAcute type A aortic dissection (AAAD) is a devastating disease. Human aortic smooth muscle cells (HASMCs) exhibit decreased proliferation and increased apoptosis, and integrin α5β1 and FAK are important proangiogenic factors involved in regulating angiogenesis. The aim of this study was to investigate the role of integrin α5β1 and FAK in patients with AAAD and the potential underlying mechanisms.MethodsAortic tissue samples were obtained from 8 patients with AAAD and 4 organ donors at Zhongshan Hospital of Fudan University. The level of apoptosis in the aortic tissues was assessed by immunohistochemical (IHC) staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays. The expression of integrin α5β1 and FAK was determined. Integrin α5β1 was found to be significantly expressed in HASMCs, and its interaction with FAK was assessed via coimmunoprecipitation (Co-IP) analysis. Proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assays and flow cytometry after integrin α5β1 deficiency.ResultsThe levels of integrin α5β1 and FAK were both significantly decreased in patients with AAAD. Downregulating the expression of integrin α5β1-FAK strongly increased apoptosis and decreased proliferation in HASMCs, indicating that integrin α5β1-FAK might play an important role in the development of AAAD.ConclusionsDownregulation of integrin α5β1-FAK is associated with increased apoptosis and decreased proliferation in aortic smooth muscle cells and may be a potential therapeutic strategy for AAAD.

Enhancing the prediction of symptomatic radiation pneumonitis for locally advanced non-small-cell lung cancer by combining 3D deep learning-derived imaging features with dose-volume metrics: atwo-center study.

This study aims to examine the ability of deep learning (DL)-derived imaging features for the prediction of radiation pneumonitis (RP) in locally advanced non-small-cell lung cancer (LA-NSCLC) patients. The study cohort consisted of 90patients from the Fudan University Shanghai Cancer Center and 59patients from the Affiliated Hospital of Jiangnan University. Occurrences of RP were used as the endpoint event. Atotal of 512 3D DL-derived features were extracted from two regions of interest (lung-PTV and PTV-GTV) delineated on the pre-radiotherapy planning CT. Feature selection was done using LASSO regression, and the classification models were built using the multilayered perceptron method. Performances of the developed models were evaluated by receiver operating characteristic curve analysis. In addition, the developed models were supplemented with clinical variables and dose-volume metrics of relevance to search for increased predictive value. The predictive model using DL features derived from lung-PTV outperformed the one based on features extracted from PTV-GTV, with AUCs of 0.921 and 0.892, respectively, in the internal test dataset. Furthermore, incorporating the dose-volume metric V30Gy into the predictive model using features from lung-PTV resulted in an improvement of AUCs from 0.835 to 0.881 for the training data and from 0.690 to 0.746 for the validation data, respectively (DeLong p < 0.05). Imaging features extracted from pre-radiotherapy planning CT using 3D DL networks could predict radiation pneumonitis and may be of clinical value for risk stratification and toxicity management in LA-NSCLC patients. Integrating DL-derived features with dose-volume metrics provides apromising noninvasive method to predict radiation pneumonitis in LA-NSCLC lung cancer radiotherapy, thus improving individualized treatment and patient outcomes.

Development and validation of predictive models for myopia onset and progression using extensive 15-year refractive data in children and adolescents

BackgroundGlobal myopia prevalence poses a substantial public health burden with vision-threatening complications, necessitating effective prevention and control strategies. Precise prediction of spherical equivalent (SE), myopia, and high myopia onset is vital for proactive clinical interventions.MethodsWe reviewed electronic medical records of pediatric and adolescent patients who underwent cycloplegic refraction measurements at the Eye & Ear, Nose, and Throat Hospital of Fudan University between January 2005 and December 2019. Patients aged 3–18 years who met the inclusion criteria were enrolled in this study. To predict the SE and onset of myopia and high myopia in a specific year, two distinct models, random forest (RF) and the gradient boosted tree algorithm (XGBoost), were trained and validated based on variables such as age at baseline, and SE at various intervals. Outputs included SE, the onset of myopia, and high myopia up to 15 years post-initial examination. Age-stratified analyses and feature importance assessments were conducted to augment the clinical significance of the models.ResultsThe study enrolled 88,250 individuals with 408,255 refraction records. The XGBoost-based SE prediction model consistently demonstrated robust and better performance than RF over 15 years, maintaining an R2 exceeding 0.729, and a Mean Absolute Error ranging from 0.078 to 1.802 in the test set. Myopia onset prediction exhibited strong area under the curve (AUC) values between 0.845 and 0.953 over 15 years, and high myopia onset prediction showed robust AUC values (0.807–0.997 over 13 years, with the 14th year at 0.765), emphasizing the models' effectiveness across age groups and temporal dimensions on the test set. Additionally, our classification models exhibited excellent calibration, as evidenced by consistently low brier score values, all falling below 0.25. Moreover, our findings underscore the importance of commencing regular examinations at an early age to predict high myopia.ConclusionsThe XGBoost predictive models exhibited high accuracy in predicting SE, onset of myopia, and high myopia among children and adolescents aged 3–18 years. Our findings emphasize the importance of early and regular examinations at a young age for predicting high myopia, thereby providing valuable insights for clinical practice.

Diagnosis of single umbilical artery and risk of foetal congenital malformations by prenatal ultrasound: a retrospective study

BackgroundSingle umbilical artery (SUA) is strongly associated with foetal structural abnormalities; however, the exact pattern of this association has not been described. We aimed to investigate the occurrence of malformations in singleton pregnancies with SUA in China and to study the association between the absent side of the umbilical artery and foetal malformations.MethodsThis was a retrospective study of singleton pregnancies for which routine first-trimester anatomical screening was performed at 11+ 0-13+ 6 gestational weeks and, if the pregnancy continued, a second-trimester scan was performed at 20+ 0-24+ 0 weeks. Data were extracted from records at the referral centre, the Obstetrics and Gynecology Hospital of Fudan University, between January 2011 and April 2019 (n = 47,894). Using logistic regression, the odds ratios (OR) with 95% confidence intervals (CIs) were calculated for malformations associated with SUA.ResultsThe incidence of SUA in our study was 2.0% (970/47,894). Of all foetuses with SUA, 387 (39.9%) had structural malformations. The malformation type varied, with cardiovascular complications being the most common. A robust association was observed between SUA and oesophageal stenosis or atresia (OR: 25.33), followed by cardiovascular (OR: 9.98–24.02), scoliosis (OR: 18.62), genitourinary (OR: 2.45–15.66), and brain malformations (OR: 4.73–9.12). The absence of the left umbilical artery (n = 445, 45.9%) was consistent with that of the right umbilical artery (n = 431, 44.4%). Furthermore, a significantly higher rate of an absent right than the left umbilical artery (p<0.01) was observed in SUA with foetal abnormalities than in SUA with no malformations.ConclusionsOverall, we observed a higher risk of various specific malformations in foetuses with SUA, and a strong association between SUA and oesophageal stenosis or atresia. The absence of the right umbilical artery was most common in foetuses with SUA and structural malformations. This study provides a reference for ultrasonographers in conducting foetal structural screening for pregnant women with SUA.