[Comparison of the efficacy of gasless robotic surgery through transaxillary apporach and open surgery for papillary thyroid carcinoma].

Objective: To compare the efficacy of gasless robotic surgery through transaxillary approach and open surgery for papillary thyroid carcinoma (PTC). Methods: The data of patient undergoing robotic surgery through transaxillary approach and traditional open surgery for PTC at the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from November 2016 to June 2023 were retrospectively analyzed. A 1∶1 propensity score matching (PSM) was performed to balance age, sex, extent of surgery, tumor size, capsule invasion, and multifocality. Surgical data, postoperative pathological data, complications, postoperative 2-month visual analog scale (VAS) scores for aesthetics, and follow-up data were compared between the two groups. Results: A total of 728 PTC patients were included. There were 339 patients in the robotic group, among which 262 were female (77.3%) and 77 were male (22.7%), with the age of [M (Q1, Q3)] 39 (32, 46) years and a body mass index (BMI) of 22.8 (20.7, 25.0) kg/m². Meanwhile, 389 patients were in the open group, among which 290 were female (74.6%) and 99 were male (25.4%), with the age of 47 (38, 55) years and a BMI of 23.2 (21.3, 25.5) kg/m2. Further analysis after PSM (there were 264 cases in both groups) showed that in the subtotal thyroidectomy and central neck dissection (LT+CCND) subgroup, the robotic group had longer operative time, higher blood loss, and greater drainage volume compared with the open group [100 (80, 130) min vs 60 (50, 80) min; 10 (10, 20) ml vs 10 (10, 20) ml; 103 (69, 145) ml vs 75 (57, 98) ml; all P<0.001], and the central lymph node metastasis rate was higher in the robotic group [45.6% (57/125) vs 31.8% (47/148), P=0.019]. In the total thyroidectomy and central neck dissection (TT+CCND) subgroup, the robotic group also had longer operative time, higher blood loss, and greater drainage volume compared with the open group [150 (110, 180) min vs 85 (75, 100) min; 20 (10, 20) ml vs 10 (10, 20) ml; 155 (107, 206) ml vs 90 (70, 120) ml; all P<0.001]. The incidence of chest skin numbness at 3 months postoperatively was higher in the robotic group compared with the open group (12.9% vs 0, P<0.001), while there were no statistically significant differences in other postoperative complications (all P>0.05). The VAS score at 2 months postoperatively was higher in the robotic group compared with the open group [9 (9, 9) vs 8 (7, 9), P<0.001]. Three cases of contralateral lobe recurrence occurred in the open group, while there were no case of recurrence in the robotic group. The 5-year overall survival rate was 100.0% in both the robotic and open groups, and there was no statistically significant difference in the 5-year disease-free survival rate between the robotic and open groups (100.0% vs 98.6%, P=0.068). Conclusion: Gasless robotic surgery through transaxillary approach for total thyroidectomy or lobectomy in the treatment of PTC is safe, feasible, and effective, with good cosmetic outcomes and comparable efficacy to traditional surgery.

[Functional analysis of laparoscopic intracorporeal Xing's neobladder in long-term follow-up].

Evaluation of neobladder function in patients with long-term survival and no recurrence after laparoscopic radical cystectomy and intracorporeal Xing's neobladder. The clinical data of laparoscopic radical cystectomy and intracorporeal Xing's neobladder in long-term survival patients with bladder cancer treated in Beijing Chaoyang Hospital from July 2013 to July 2018 were analyzed retrospectively. All 17 patients underwent the surgery by the same surgical team, including 15 males and 2 females, whose mean age at the time of operation was (55.9±7.6) years. Thepostoperative urinary function and renal function were summarized. All operations were successfully completed. The mean operative time was (340±62) min. All patients were followed up for a long time, with a median follow-up time of 80(70, 96) months, Urinary continence was achieved in 17 (100%)casesduring the day and 13 (76.5%) cases at night, with a median bladder volume of 350 (200, 400) ml. All patients had good urinary control after surgery, and no hydronephrosis or creatinine increase was found in reexamination.After the application of Xing's neobladder operation, the patient maintained acceptable urinary control status after the operation, and the long-term follow-up effect was satisfactory.

[Research progress on electromyographic methods for sustained low-intensity muscle fatigue detection].

Sustained low-intensity muscle fatigue (SULMF) refers to the phenomenon that skeletal muscle continues to contract at less than 10% of maximum voluntary contraction during work activities, resulting in decreased muscle contractile function, which is one of the main causes of occupational neck, shoulder, waist and back discomfort and pain symptoms. Although surface electromyography is a key physiological technique for assessing the efficiency of neuromuscular activity, its effectiveness in objectively detecting SULMF remains controversial. Therefore, this paper describes the neurophysiological mechanism and related hypotheses of SULMF, and reviews the research progress of electromyography detection indicators and detection methods of SULMF, which is of great significance for the early prevention and accurate detection of work-related musculoskeletal disorders.

[Construction of CD138-targeted chimeric antigen receptor- modified T cells and their effect in multiple myeloma therapy].

Objective: To construct a novel chimeric antigen receptor T (CAR-T) cell targeting CD138 and to investigate its cytotoxicity against myeloma cells. Methods: The hybridoma strain that can stably secrete the CD138 monoclonal antibody (mAb) was prepared and obtained through monoclonal antibody screening technology. The hybridoma strain cells were intraperitoneally injected into mice to produce ascites containing monoclonal antibodies, which were then collected and purified to obtain pure CD138 mAb. Further examinations were performed to assess the biological characteristics of CD138 mAb. The variable region sequence of this antibody was amplified through reverse transcription polymerase chain reaction and was used as the antigen recognition domain of CD138 CAR, which was subsequently expressed on the surface of T cells by lentiviral infection. Flow cytometry was employed to assess the phenotype of CD138 CAR-T cells. In vitro cytotoxicity and degranulation assays were performed to evaluate their antitumor effects. Results: ① We successfully prepared anti-human CD138 antibody hybridoma cell lines and screened a hybridoma cell strain, 5G2, which could persistently and stably secrete the anti-CD138 antibody. ② The purified CD138 (5G2) mAb can especially recognize CD138(+) cells with a binding affinity constant (K(D)) of 6.011×10(-9) mol/L and showed no significant binding activity with CD138(-) cells. ③The variable region sequence of the CD138 (5G2) antibody was obtained using molecular cloning technology, and CD138 (5G2) CAR was successfully constructed and expressed on T cells through lentivirus infection and, concurrently, demonstrated effective binding to recombinant human CD138 protein.④ The proliferation of T cells transduced with the CD138 (5G2) CAR was highly efficient. The phenotype analysis revealed that CD138 (5G2) CAR-T cells exhibited a greater tendency to differentiate into central memory T cells and memory stem T cells, with a reduced proportion of terminally differentiated effector memory subsets. ⑤CD138 (5G2) CAR-T cells demonstrated specific cytotoxicity against CD138(+) myeloma cell line H929, whereas CD138(-) cell line K562 remained unaffected. The percentage of residual H929 cells was (12.92±8.02) % after co-culturing with CD138 (5G2) CAR-T cells, while (54.25±15.79) % was left in the Vector-T group (E∶T=1∶2; P<0.001). ⑥Results of degranulation assays demonstrated a significant activation of CD138 (5G2) CAR-T cells after co-culture with the H929 cell line, whereas no significant activation was observed in Vector-T cells [ (25.78±3.35) % vs (6.13±1.30) %, P<0.001]. ⑦After co-culturing with CD138(+) cells, CD138 (5G2) CAR-T cells exhibited a significant increase in cytokine secretion compared to the Vector-T group [interleukin-2: (1 697.52±599.05) pg/ml vs (5.07±1.17) pg/ml, P<0.001; interferon-γ: (3 312.20±486.38) pg/ml vs (9.28±1.46) pg/ml, P<0.001; and tumor necrosis factor-α: (1 837.43±640.49) pg/ml vs (8.75±1.65) pg/ml, P<0.001]. However, no significant difference was observed in cytokine secretion levels between the two groups after co-culturing with CD138(-) cells. Conclusion: This study successfully prepared a novel monoclonal antibody against CD138, and CAR-T cells constructed with the antigen recognition domain derived from this 5G2 mAb demonstrated effective antitumor activity against myeloma cells. This can be used as a new option for the detection of the CD138 antigen and proposes a novel strategy for multiple myeloma immunotherapy.

[The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation].

Objective: To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured. Results: After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) (P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) (P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0-15 989) (P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 (P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions: The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

[Two cases of systemic mastocytosis with RUNX1-RUNX1T1 positive acute myeloid leukemia treated with sequential avapritinib after allogeneic hematopoietic stem cell transplantation and literature review].

Systemic mastocytosis (SM) with RUNX1-RUNX1T1 positive acute myeloid leukemia (AML) is a rare myeloid tumor with no standard treatment. Two cases of SM patients with RUNX1-RUNX1T1 positive AML treated with sequential avapritinib after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were reported in Henan Cancer Hospital. Mast cell in bone marrow disappeared, C-KIT mutation and RUNX1-RUNX1T1 fusion gene remained negative. Allo-HSCT sequential avapritinib is an effective treatment for SM patients with RUNX1-RUNX1T1 positive AML.

Lacticaseibacillus rhamnosus LRa05 alleviated liver injury in mice with alcoholic fatty liver disease by improving intestinal permeability and balancing gut microbiota.

This study investigated the effect of Lacticaseibacillus rhamnosus LRa05 on alcoholic fatty liver disease (ALD) and its mechanism for liver protection. Mice were randomly divided into three groups: a control (CLT) group, an ALD group, and a LRa05 intervention group. The ALD mouse model was established by Lieber-DeCarli chronic alcohol feeding. Tissues staining, enzyme-linked immunosorbent assay (ELISA) was performed to detect changes in histopathology and inflammatory cytokines, respectively. Moreover, intestinal permeability was evaluated by the level of dextran-fluorescein isothiocyanate (Dx-FITC) in serum and tight junction protein in the colon. Changes in the composition of the gut microbiota were assessed by 16S rRNA sequencing. Alcohol consumption induced liver damage in mice with significantly increased levels of triglycerides (TG), aspartate aminotransferase (AST), alanine transaminase (ALT), and inflammatory cytokines. Moreover, alcohol further induced the increase of intestinal permeability and disruption of gut microbiota in mice, with an increase in the relative abundance of potentially pathogenic bacteria Enterococcus, Parabacteroides, and Alistipes. LRa05 intervention significantly attenuated alcohol-induced liver injury by reducing the contents of TG, ALT, and AST, and suppressing the inflammatory responses. Meanwhile, by stimulating the expression of ZO-1, Occludin, and Claudin in the colon tissue, LRa05 additionally strengthened the intestine barrier function. Furthermore, gut microbiota analysis suggested that LRa05 partially ameliorated gut microbiota disorders in ALD mice and up-regulated the abundance of Desulfovibrio and Akkermansia, which were negatively correlated with the indicators of ALD progression. The reconstructive effects of LRa05 on the gut microbiota might be related to the efficacy of LRa05 in improving gut permeability and further protecting against ALD.

[Clinicopathological features and prognosis of sporadic mismatch repair deficient colorectal cancer].

Objective: To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer. Methods: A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate. Results: Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side (P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion: For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

[Diagnostic and intervention value of implantable cardiac monitor in patients over 60 years of age with unexplained syncope].

Objective: To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope. Methods: This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan-Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope. Results: A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group (HR=11.66, 95%CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions: ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

[Treatment of Fournier's gangrene with "firebreak" drainage based on skin preservation].

Objective: To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene. Methods: This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation. Results: All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days. Conclusions: The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.

Global Burden of Dementia Death from 1990 to 2019, with Projections to 2050: An Analysis of 2019 Global Burden of Disease Study.

BACKGROUND: Dementia is a growing global health challenge. Quantifying the current burden and predicting the future increases of dementia-related deaths are necessary to enhance effective policy decisions and health system planning. METHODS: Data on dementia mortality was derived from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study. The 2020-2050 dementia-related deaths were forecasted using the Bayesian age-period-cohort model. RESULTS: Globally, the number of dementia-related death increased from 0.56 million in 1990 to 1.62 million in 2019 and were estimated to increase to 4.91 million by the year 2050. Metabolic risk factors would become the most important modifiable risk factors affecting dementia death which account for 28.10% of dementia related death by the year 2050. For different Socio-demographic Index (SDI) regions, the low SDI region would have the highest age-standardized mortality rate (ASMR) (29.16 per 100,000) by 2050. Moreover, the number of dementia-related deaths under the age of 70 years was predicted to reach 0.18 million by 2050. CONCLUSIONS: Dementia related death remains a global health problem, and health policies targeting metabolic risk factors may be an important way to alleviate this problem.

Prediction of Alzheimer's Disease Based on 3D Genome Selected circRNA.

Alzheimer's disease (AD) is a neurodegenerative disease and there is by far no effective treatment for it, especially in its late stage. Circular RNAs (circRNAs), known as a class of non-coding RNAs are widely observed in eukaryotic transcriptomes, and are reported to play an important role in neurodegenerative diseases including AD. circRNAs usually act as microRNA (miRNA) inhibitors or «sponges¼ to regulate the function of miRNAs, leading to subsequent changes in protein activities and functions. Accumulating evidence indicates that circRNAs can serve as potential biomarker in AD early prediction. The functional roles of circRNAs are very versatile including miRNAs binding - thus affecting downstream gene expression, generating abnormally translated protein peptides, and affecting epigenetic modifications which subsequently affect AD related gene expressions. Therefore, identifying AD-related circRNAs can contribute to AD early diagnosis and intervention. In this work, we collected and curated an AD-related circRNA dataset; by exploring the circRNAs' corresponding DNA loci distribution in chromatin 3D conformation (3D genome) and utilize the such 3D genome information, we were able to selected a concise yet predictively effective circRNA panel, based on which, significantly better AD prediction machine learning models were achieved.

Association between Resting Heart Rate and Machine Learning-Based Brain Age in Middle- and Older-Age.

BACKGROUND: Resting heart rate (RHR), has been related to increased risk of dementia, but the relationship between RHR and brain age is unclear. OBJECTIVE: We aimed to investigate the association of RHR with brain age and brain age gap (BAG, the difference between predicted brain age and chronological age) assessed by multimodal Magnetic Resonance Imaging (MRI) in mid- and old-aged adults. DESIGN: A longitudinal study from the UK Biobank neuroimaging project where participants underwent brain MRI scans 9+ years after baseline. SETTING: A population-based study. PARTICIPANTS: A total of 33,381 individuals (mean age 54.74 ± 7.49 years; 53.44% female). MEASUREMENTS: Baseline RHR was assessed by blood pressure monitor and categorized as <60, 60-69 (reference), 70-79, or ≥80 beats per minute (bpm). Brain age was predicted using LASSO through 1,079 phenotypes in six MRI modalities (including T1-weighted MRI, T2-FLAIR, T2*, diffusion-MRI, task fMRI, and resting-state fMRI). Data were analyzed using linear regression models. RESULTS: As a continuous variable, higher RHR was associated with older brain age (ß for per 1-SD increase: 0.331, 95% [95% confidence interval, CI]: 0.265, 0.398) and larger BAG (ß: 0.263, 95% CI: 0.202, 0.324). As a categorical variable, RHR 70-79 bpm and RHR ≥80 bpm were associated with older brain age (ß [95% CI]: 0.361 [0.196, 0.526] / 0.737 [0.517, 0.957]) and larger BAG (0.256 [0.105, 0.407] / 0.638 [0.436, 0.839]), but RHR< 60 bpm with younger brain age (-0.324 [-0.500, -0.147]) and smaller BAG (-0.230 [-0.392, -0.067]), compared to the reference group. These associations between elevated RHR and brain age were similar in both middle-aged (<60) and older (≥60) adults, whereas the association of RHR< 60 bpm with younger brain age and larger BAG was only significant among middle-aged adults. In stratification analysis, the association between RHR ≥80 bpm and older brain age was present in people with and without CVDs, while the relation of RHR 70-79 bpm to brain age present only in people with CVD. CONCLUSION: Higher RHR (>80 bpm) is associated with older brain age, even among middle-aged adults, but RHR< 60 bpm is associated with younger brain age. Greater RHR could be an indicator for accelerated brain aging.

Biomarkers and Cognition Study, Singapore (BIOCIS): Protocol, Study Design, and Preliminary Findings.

BACKGROUND: The focus of medicine is shifting from treatment to preventive care. The expression of biomarkers of dementia and Alzheimer's disease (AD) appear decades before the onset of observable symptoms, and evidence has emerged supporting pharmacological and non-pharmacological interventions to treat modifiable risk factors of dementia. However, there is limited research on the epidemiology, clinical phenotypes, and underlying pathobiology of cognitive diseases in Asian populations. OBJECTIVES: The objectives of the Biomarkers and Cognition Study, Singapore(BIOCIS) are to characterize the underlying pathobiology of Cognitive Impairment through a longitudinal study incorporating fluid biomarker profiles, neuroimaging, neuropsychological and clinical outcomes in a multi-ethnic Southeast Asian population. DESIGN, SETTING, PARTICIPANTS: BIOCIS is a 5-year longitudinal study where participants are assessed annually. 2500 participants aged 30 to 95 will be recruited from the community in Singapore. To investigate how pathology presents with or without minimal clinical symptoms and vice versa, CI and unimpaired individuals will be recruited. Participants will undergo assessments to characterise biomarkers of dementia through neuroimaging, fluid biomarkers, cognitive assessments, behavioural and lifestyle profiles, retinal scans and microbiome indicators. RESULTS: Since commencement of recruitment in February 2022, 1148 participants have been enrolled, comprising 1012 Chinese, 62 Indian, and 35 Malay individuals. Mean age and education is 61.32 years and 14.34 years respectively with 39.8% males. 47.9 % of the cohort are employed and 32.06% have a family history of dementia. The prevalence of cerebral small vessel disease is 90.2% with a mean modified Fazekas white matter hyperintensity score of 4.1. CONCLUSION: The BIOCIS cohort will help identify novel biomarkers, pathological trajectories, epidemiology of dementia, and reversible risk factors in a Southeast Asian population. Completion of BIOCIS longitudinal data could provide insights into risk-stratification of Asians populations, and potentially inform public healthcare and precision medicine for better patient outcomes in the prevention of Alzheimer's disease and dementia.

[Clinical analysis of the correlation between the expression of soluble B cell maturation antigen and the efficacy of chimeric antigen receptor T cell targeting B cell maturation antigen in patients with multiple myeloma].

Objective: The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) . Methods: This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared. Results: ①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD (P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM (R(2)=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion: sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.