[Surgical treatment and prognosis analysis of hilar cholangiocarcinoma].

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

[Application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection in the sphincter-preserving resection of low rectal cancer].

Objectives: To investigate the application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection (LDER) in the anal preservation treatment of low rectal cancer. Methods: Inclusion criteria: (1) age was 18-70; (2) the distance of the lower tumor edge from the anal verge was 4-5 cm; (3) primary tumor with a diameter ≤3 cm; (4) preoperative staging of T1~2N1~2M0; (5) "difficult pelvis", defined as ischial tuberosity diameter<10 cm or body mass index>25 kg/m2; (6) patients with strong intention for sphincter preservation; (7) no preoperative treatment (e.g., chemotherapy, radiotherapy, molecular targeted therapy, or immunotherapy); (8) no lateral lymph node enlargement; (9) no previous anorectal surgery; (10) patients with good basic condition who could tolerate surgery. Exclusion criteria: (1) previously suffered from malignant tumors of the digestive tract or currently suffering from malignant tumors out of the digestive tract; (2) patients with preoperative anal dysfunction (Wexner score ≥ 10), or fecal incontinence. The specific surgical steps are as follows: the distal end of the rectum was dissected to the level of the interspace between internal and external sphincters of anal canal. Five centimeters proximal to the tumor, the mesorectum was ligated, and a liner stapler was used to transect the rectum. The distal rectum with the tumor were then everted and extracted through the anus. The rectum was transected 0.5-1.0 cm distal to the tumor with a linear stapler. Full thickness suture was used to reinforce the stump of the rectum, which was then brought back into the pelvic cavity. Finally, an end-to-end anastomosis between the colon and the rectum was performed. A retrospective descriptive study was performed of the clinical and pathological data of 12 patients with T1-T2 stage low rectal cancer treated with LDER at Henan Provincial People's Hospital from January 2020 to December 2022. Results: All 12 patients successfully completed LDER with sphincter preservation, without conversion to open surgery or changes in surgical approach. The median surgical time was 272 (155-320) minutes, with a median bleeding volume of 100 (50-200) mL. No protective stoma was performed, and all patients received R0 resection. The average hospital stay was 9 (7-15) days. There were no postoperative anastomotic leakage or perioperative deaths. All 12 patients received postoperative follow-up, with a median follow-up of 12 months (6-36 months) and a Wexner score of 8 (5-14) at 6 months postoperatively. There was no tumor recurrence or metastasis during the follow-up period. Conclusions: LDER is safe and effective for the treatment of low rectal cancer.

Hearing Screening in High-Risk Neonates Using Distortion Product Oto-Acoustic Emission.

The prevalence of hearing loss is 0.09-2.3% in low risk neonates, and 0.3-14.1% in the high-risk population. The treatment requires early identification by neonatal hearing screening and early rehabilitation. OAE (oto-acoustic emission) and ABR (Auditory Brain Response) are the two objective tests used to evaluate hearing loss in neonates. OAE tests the biological response of the cochlea to auditory stimuli. ABR tests the auditory pathway. The aim is to estimate hearing loss in high-risk neonates using the Distortion Product Oto- acoustic emission (DP OAE) and to correlate the associated high-risk factors. This was a cross-sectional study conducted between March 2021 to September 2022. Newborns satisfying the inclusion criteria were included in the study. DP- OAE is performed to screen for hearing loss within 48 h of birth. Infants failing the first screening test are then examined for treatable causes and then repeated at 2 weeks. Newborns who fail the second DP-OAE are subjected to ABR for confirmation of hearing loss. A total of 100 high risk neonates underwent hearing screen using DP-OAE. Most common risk factors seen in our study are prematurity (22%), Low birth weight (< 2.5 kg) (20%), Neonatal Hyperbilirubinemia (17%), Maternal risk factors (GDM) (14%). Most neonates with prematurity failed the hearing test with significant p-value of 0.05. DP- OAE test can be successfully implemented as newborn hearing screening method, for early detection of hearing impairment to achieve the high quality standard of screening programs.

Primary perineal endometriosis - a case report and literature review.

Endometriosis is a common gynecological disease caused by the implantation of active endometrial cells outside the uterine cavity. In most cases, endometriosis occurs in the pelvic area, such as the ovary, Douglas' pouch, or uterine sacral ligament. Some rare cases of extrapelvic endometriosis can also occur in the perineum, urinary system, gastrointestinal tract, nervous system, chest, subcutaneous tissue, and skin. Endometriosis of the perineum is usually secondary to obstetric trauma, such as perineal laceration or episiotomy. To date, few cases of spontaneous perineal endometriosis have been reported. Herein, we report a rare case of spontaneous deep perineal endometriosis. Notably, the patient had typical symptoms of regular pain during menstruation with no history of delivery or perineal trauma. The patient recovered well after postoperative gonadotropin releasing hormone agonist injection.

[Alteration and significance of serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma: a retrospective study based on LEGEND-2].

Objective: To explore the dynamic changes in serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma (R/R MM) based on LEGEND-2. Methods: The data of patients with R/R MM who underwent BCMA-CAR-T therapy at our hospital between March 30, 2016, and February 6, 2018, were retrospectively collected. Serum lipid levels, controlled nutritional status (CONUT) score, and other clinical indicators at different time points before and after CAR-T-cell infusion were compared and analyzed. The best cut-off value was determined by using the receiver operator characteristic (ROC) curve. The patients were divided into high-CONUT score (>6.5 points, malnutrition group) and low-CONUT score groups (≤6.5 points, good nutrition group), comparing the progression-free survival (PFS) and total survival (OS) of the two groups using Kaplan-Meier survival analysis. Results: Before the infusion of CAR-T-cells, excluding triglycerides (TG), patients' serum lipid levels were lower than normal on average. At 8-14 d after CAR-T-cell infusion, serum albumin (ALB), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apolipoprotein A1 (Apo A1) levels dropped to the minimum, whereas CONUT scores reached the maximum. In addition to TG, apolipoprotein B (Apo B) levels increased compared with baseline. After CAR-T-cell therapy, the patients' serum lipid levels significantly increased with well-improved nutritional status. Spearman's related analysis showed that TC, HDL, and ApoA1 levels after CAR-T-cell injection were significantly negatively correlated with the grade of cytokine-release syndrome (CRS) (r=-0.548, P=0.003; r=-0.444, P=0.020; r=-0.589, P=0.001). Furthermore, survival analysis indicated that the CONUT score was unrelated to PFS, and the median OS of patients with R/R MM in the high-CONUT score group was shorter than that in the low-CONUT score group (P=0.046) . Conclusions: During CAR-T-cell therapy, hypolipidemia and poor nutritional status were aggravated, which is possibly related to CRS. The patients' serum lipid levels and nutritional status were significantly improved after CAR-T-cell treatment. The CONUT score affected the median OS in patients treated with CAR-T-cells. Therefore, specific screening and intervention for nutritional status in patients receiving CAR-T-cell therapy are required.

Psychometric evaluation of the electronic faces thermometer scale for pain assessment in children 8-17 years old: A study protocol.

It is often a challenge for a child to communicate their pain, and their possibilities to do so should be strengthened in healthcare settings. Digital self-assessment provides a potential solution for person-centered care in pain management and promotes child participation when a child is ill. A child's perception of pain assessment differs when it is assessed using digital or analog formats. As we move into the digital era, there is an urgent need to validate digital pain assessment tools, including the newly developed electronic Faces Thermometer Scale (eFTS). This study protocol describes three studies with the overall aim to evaluate psychometric properties of the eFTS for assessing pain in children 8-17 years of age. A multi-site project design combining quantitative and qualitative methods will be used for three observational studies. Study 1: 100 Swedish-speaking children will report the level of anticipated pain from vignettes describing painful situations in four levels of pain and a think-aloud method will be used for data collection. Data will be analyzed with phenomenography as well as descriptive and comparative statistics. Study 2: 600 children aged 8-17 years at pediatric and dental settings in Sweden, Denmark, Iceland, and USA will be included. Children will assess their pain intensity due to medical or dental procedures, surgery, or acute pain using three different pain Scales for each time point; the eFTS, the Faces Pain Scale Revised, and the Coloured Analogue Scale. Descriptive and comparative statistics will be used, with subanalysis taking cultural context into consideration. Study 3: A subgroup of 20 children out of these 600 children will be purposely included in an interview to describe experiences of grading their own pain using the eFTS. Qualitative data will be analyzed with content analysis. Our pilot studies showed high level of adherence to the study procedure and rendered only a small revision of background questionnaires. Preliminary analysis indicated that the instruments are adequate to be used by children and that the analysis plan is feasible. A digital pain assessment tool contributes to an increase in pain assessment in pediatric care. The Medical Research Council framework for complex interventions in healthcare supports a thorough development of a new scale. By evaluating psychometric properties in several settings by both qualitative and quantitative methods, the eFTS will become a well-validated tool to strengthen the child's voice within healthcare.

Evaluation of Improvement in Chronic Rhinosinusitis After Endoscopic Sinus Surgery Using Sino-Nasal Outcome Test-22 (SNOT22) Symptom Score.

Sino-Nasal Outcome Test (SNOT-22) symptom score is the most widely used questionnaire due to its easy interpretation with respect to quality of life (QOL) in patients with chronic rhinosinusitis (CRS). It helps in deciding further treatment plan in patients with refractory CRS despite maximal medical therapy (MMT). Endoscopic sinus surgery (ESS) is suggested in patients not responding to medical treatment. The preoperative and post-operative QOL for patients with CRS is assessed using SNOT-22. To assess SNOT-22 score change in CRS resistant to MMT. This is a longitudinal study conducted from April 2021-September 2022 included patients diagnosed to have CRS, satisfying the inclusion criteria. SNOT-22 for symptom severity assessed at the first visit, 1 week and 12 weeks and after MMT. Patients who failed MMT, posted for ESS. Post-operatively SNOT-22 symptom score re-assessed at 15 days, 1 month, 2 months and 3 months. 56 patients (male-51% and female-49%) who failed to respond to MMT included in the study. The five major troublesome symptoms nasal blockage (92.86%), need to blow nose (75%), facial pressure/pain (53.57%), post nasal discharge (51.79%), and sneezing (42.86%). The mean SNOT-22 symptom score when compared with pre-operatively (69.54 ± 8.973) and after FESS (2.09 ± 1.881) had improved significantly (p < 0.001). CRS is more frequently seen in males aged between 21 and 30 years. The patient-based outcome measures, like SNOT-22 helps to foresee the extent of post- operative improvement. The effective management of CRS is by surgical intervention.

[Clinical and laboratory features of SF3B1-mutated myeloproliferative neoplasms].

Objective: To explore the clinical and laboratory characteristics of SF3B1 gene mutations in myeloproliferative neoplasms (MPN) patients. Methods: The clinical data of 273 MPN patients who were diagnosed MPN and treated in the Second Hospital of Tianjin Medical University from November 2017 to March 2023 were retrospectively analyzed. There were 133 males and 140 females, with a median age M(Q1,Q3)of 56(46, 67) years. The molecular biology and cytogenetic characteristics were detected by second-generation sequencing (NGS) and R+G banding techniques, and the clinical and laboratory characteristics of patients with SF3B1 gene mutation were analyzed. Results: SF3B1 gene mutations were found in 13 patients (4.8%, 13/273).The types of SF3B1 mutations included missense (92.3%, 12/13) and nonsense mutations (7.7%, 1/13).Compared to the non-mutant cohort, patients in SF3B1 mutant cohort had older ages [68(51, 76) vs 56(45, 66)years,P=0.025], higher proportion of splenomegaly [46.2%(6/13) vs 15.8%(41/259),P=0.014]and secondary tumor [23.1%(3/13)vs 3.8%(10/260), P=0.018]with higher proportion of bone marrow blast [0.5%(0, 1.5%) vs 0(0, 0.5%),P=0.002] and lower hemoglobin[(104±36) vs (137±40) g/L,P=0.004] and hematocrit [31%(22%, 40%) vs 41%(35%, 52%),P=0.003]. All of the 10 patients in the SF3B1 mutant cohort whose ring sideroblast (RS) could be evaluated showed no RS formation. The overall survival, thrombosis-free survival and leukemia free survival of MPN patients in SF3B1 mutant cohort were 4.0 (2.0, 6.0), 2.0 (0.5, 4.5) and 4.0 (2.0, 6.0) years, respectively, while patients in the non-mutant cohort were 6.0 (3.0, 10.0), 5.0 (1.0, 8.0), 6.0 (3.0, 10.0) years, respectively, there were no statistical significance between two groups (Z=3.69, 1.66, 2.05, all P>0.05).The secondary tumor free survival of SF3B1 mutant cohort patients was 4.0 (2.0, 6.0) years, which was lower than that of non-mutant cohort patients [5.5 (3.0, 10.0) years, Z=18.18, P<0.001). Conclusions: MPN patients with SF3B1 gene mutations are older, more prone to splenomegaly and secondary tumors. They also have a higher proportion of bone marrow blast, lower hemoglobin and hematocrit, and show no RS formation.

[Research status and challenges of advanced myeloproliferative neoplasms].

Classical myeloproliferative neoplasms (MPN), also known as Ph-MPN, includes polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Secondary myelofibrosis (sMF) and secondary acute myeloid leukemia (sAML) are important disease progressions of MPN. After MPN disease progression, hematopoietic stem cells undergo new clonal evolution, leading to drug resistance, poor treatment effect and poor survival of patients. In recent years, the exploration of the mechanism of disease progression and the precise diagnosis and treatment of MPN have attracted much attention. This article summarizes the research status of MPN disease progression, including the pathogenesis, risk stratification, and precision treatment, in order to provide reference for exploring new diagnosis and treatment methods of MPN disease progression.

[Efficacy and safety of pegylated interferon alpha-2b for patients with myeloproliferative neoplasm].

Objective: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG-IFN-α2b) in the treatment of myeloproliferative neoplasm (MPN). Methods: Thirty-four MPN patients receiving PEG-IFN-α2b treatment in the Second Hospital of Tianjin Medical University from August 2019 to October 2022 were prospectively included. Among the patients, 9 were male and 25 were female, and the median age [M (Q1, Q3)] was 57 (19, 78) years. Patients' clinical characteristics were collected and the follow-up was performed. As of January 30, 2023, the follow-up period [M(Q1, Q3)] was 24 (16, 33) months. The efficacy, safety and changes in immune cell and cytokine levels after 12 and 24 months of treatment were analyzed. Results: During the follow-up period, 4 patients dropped out, and the efficacy was evaluable in 30 patients. Following 12 and 24 months of treatment, the complete hematologic response (CHR) rates were 57.1% (16/28) and 75.0% (18/24), respectively. The complete molecular response (CMR)+partial molecular response (PMR) rates were 27.3% (6/22) and 55.0% (11/20), respectively. The bone marrow histopathological overall response rates (ORR) were 34.6% (9/26) and 47.6% (10/21), respectively. At 12 and 24 months of treatment, the proportions of CD8+HLA-DR+T cells, effector T cell subpopulations, CD56bright natural killer (NK) cells, and plasmacytoid dendritic cells (pDC) were higher than the pre-treatment levels, while the proportion of CD56dim NK cells was lower than the pre-treatment level (all P<0.05). The levels of motif chemokine ligand 10 (CXCL10), tumor necrosis factor (TNF)-α and TNF-ß in bone marrow all increased from those prior to treatment, while the levels of vascular endothelial growth factor (VEGF) and interleukin (IL-4) decreased from those prior to treatment (all P<0.05). Among hematological adverse reactions, white blood cells decrease [47% (16/34)] was observed with high incidence. Among non-hematological adverse reactions, asthenia [44.1% (15/34)] and transaminases increase [32.3% (11/34)] were observed with high incidences. Conclusions: PEG-IFN-α2b has high hematologic, molecular, and bone marrow histopathological response rates in the treatment of MPN. It can reduce malignant clone loads and regulate the immune microenvironment and is safe and well tolerated overall.

[Analysis of risk factors for thromboembolism in patients with JAK2V617F gene mutation positive myeloproliferative neoplasms].

Objective: To analyze the risk factors of thrombosis in patients with JAK2V617F mutation positive myeloproliferative neoplasms (MPN). Methods: A total of 223 MPN patients with JAK2V617F mutation in the Second Hospital of Tianjin Medical University from September 2017 to May 2023 were retrospectively enrolled, including 111 males and 112 females, aged [M(Q1,Q3)] 57(21,66) years. According to the presence or absence of thromboembolism during follow-up, the patients were divided into thrombosis group (n=102) and non-thrombosis group (n=121). The clinical characteristics, laboratory characteristics, cytogenetics and other disease progression and survival of the two groups of patients were analyzed. As of March 31, 2023, the follow-up period [M (Q1, Q3)] was 6 (3, 10) years. The influencing factors of thrombosis in JAK2V617F positive MPN patients were analyzed by using the Cox risk model. Results: Among 223 JAK2V617F positive MPN patients, 144 were polycythemia vera (PV), 51 were essential thrombocythemia (ET) and 28 were primary myelofibrosis (PMF). The mutation rates of ASXL1 and BCORL1 genes in the thrombosis group were 19.6% (20/102) and 6.9% (7/102), respectively, which were higher than those in the non-thrombosis group [9.1% (11/121) and 0.8% (1/121)] (both P<0.05). The proportion of monocytes, C-reactive protein (CRP), interleukin-1ß (IL)-1ß, IL-8 and tumor necrosis factor-ß (TNF-ß) increased in the thrombosis group were higher than those in the non-thrombosis group (all P<0.05). Multivariate analysis showed that age≥60 years (HR=2.132, 95%CI: 1.376-3.303, P=0.001), history of thrombosis (HR=3.636, 95%CI: 2.121-6.202, P<0.001), ASXL1 mutation positive (HR=2.245, 95%CI: 1.093-3.231, P=0.022) and elevated TNF-ß (HR=2.009, 95%CI: 1.113-3.624, P=0.021) were risk factors for thrombosis in JAK2V617F positive MPN patients. Conclusions: In addition to age, history of thrombosis and positive ASXL1 mutation, elevated TNF-ß is also an influencing factor of thrombosis in JAK2V617F positive MPN patients. Intervention of inflammation may have a certain effect on the prevention and treatment of thrombosis.

Allisartan Isoproxil Promotes Uric Acid Excretion by Interacting with Intestinal Urate Transporters in Hyperuricemic Zebrafish (Danio rerio).

To evaluate the urate-lowering effect and potential drug targets of antihypertensive agent allisartan isoproxil (ALI) and its bioactive metabolite EXP3174, we developed an acute hyperuricemic zebrafish model using potassium oxonate and xanthine sodium salt. Losartan potassium served as the positive control (reference drug). In this model, ALI and losartan potassium exerted a greater urate-lowering effect than EXP3174 indicating that the latter is not the critical substance for elimination of uric acid. The quantitative real-time PCR showed that ALI upregulates the expression of intestinal urate transporters genes ABCG2, PDZK1, and SLC2A9 (p<0.01). Thus, we can suggest that this substance promotes uric acid excretion mainly by interacting with intestinal urate transporters.

Floating-Point Approximation Enabling Cost-Effective and High-Precision Digital Implementation of FitzHugh-Nagumo Neural Networks.

The study of neuron interactions and hardware implementations are crucial research directions in neuroscience, particularly in developing large-scale biological neural networks. The FitzHugh-Nagumo (FHN) model is a popular neuron model with highly biological plausibility, but its complexity makes it difficult to apply at scale. This paper presents a cost-saving and improved precision approximation algorithm for the digital implementation of the FHN model. By converting the computational data into floating-point numbers, the original multiplication calculations are replaced by adding the floating-point exponent part and fitting the mantissa part with piecewise linear. In the hardware implementation, shifters and adders are used, greatly reducing resource overhead. Implementing FHN neurons by this approximation calculations on FPGA reduces the normalized root mean square error (RMSE) to 3.5% of the state-of-the-art (SOTA) while maintaining a performance overhead ratio improvement of 1.09 times. Compared to implementations based on approximate multipliers, the proposed method achieves a 20% reduction in error at the cost of a 2.8% increase in overhead.This model gained additional biological properties compared to LIF while reducing the deployment scale by only 9%. Furthermore, the hardware implementation of nine coupled circular networks with eight nodes and directional diffusion was carried out to demonstrate the algorithm's effectiveness on neural networks. The error decreased to 60% compared to the single neuron of the SOTA. This hardware-friendly algorithm allows for the low-cost implementation of high-precision hardware simulation, providing a novel perspective for studying large-scale, biologically plausible neural networks.

Effect of antioxidant procyanidin b2 (pcb2) on ovine oocyte developmental potential in response to in vitro maturation (ivm) and vitrification stress.

BACKGROUND: It was demonstrated that external stress, such as in vitro maturation (IVM) and vitrification process can induce significantly reduced development capacity in oocytes. Previous studies indicated that antioxidants play a pivotal part in the acquisition of adaptation in changed conditions. At present, the role of the natural potent antioxidant PCB2 in response to IVM and vitrification during ovine oocyte manipulation has not been explored. OBJECTIVE: To investigate whether PCB2 treatment could improve the developmental potential of ovine oocytes under IVM and vitrification stimuli. MATERIALS AND METHODS: The experiment was divided into two parts. Firstly, the effect of PCB2 on the development of oocytes during IVM was evaluated. Un-supplemented and 5 ug per mL PCB2-supplemented in the IVM solution were considered as control and experimental groups (C + 5 ug per mL PCB2). The polar body extrusion (PBE) rate, mitochondrial membrane potential (MMP), ATP, reactive oxygen species (ROS) levels and early apoptosis of oocytes were measured after IVM. Secondly, we further determine whether PCB2 could improve oocyte quality under vitrification stress. The survival rate, PBE rate and early apoptosis of oocytes were compared between fresh group, vitrified group and 5 ug per mL PCB2-supplemented in the IVM solution after vitrification (V + 5 ug per mL PCB2). RESULTS: Compared to the control group, adding PCB2 significantly increased PBE rate (79.4% vs. 62.8%, P < 0.01) and MMP level (1.9 +/- 0.08 vs. 1.3 +/- 0.04, P < 0.01), and decreased ROS level (47.1 +/- 6.3 vs. 145.3 +/- 8.9, P < 0.01). However, there was no significant difference in ATP content and early apoptosis. Compared to the fresh group, vitrification significantly reduced oocytes viability (43.0% vs. 90.8%, P < 0.01) as well as PBE rate (24.2% vs. 60.6%, P < 0.05). However, 5 ug per mL PCB2-supplemention during maturation had no effect on survival, PBE or early apoptosis in vitrified oocytes. CONCLUSION: PCB2 could effectively antagonise the oxidative stress during IVM and promote oocyte development. DOI: 10.54680/fr23210110412.

Whole genome sequencing analysis in fetal structural anomalies: novel phenotype-genotype discoveries.

OBJECTIVES: The identification of structural variants and single nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole genome sequencing (WGS) is becoming more widespread in genetic disease diagnosis. However, data on its clinical utility remain limited in prenatal practice. We aimed to expand our understanding of implementing WGS in the genetic diagnosis of fetal structural anomalies. METHODS: We employed trio WGS with a minimum coverage of 40X on the MGI DNBSEQ-T7 platform in a cohort of 17 families with fetuses presenting with aberrations detected by ultrasonography but uninformative findings of standard chromosome microarray analysis (CMA) and exome sequencing (ES) testing. RESULTS: Causative genetic variants were identified in two families with a diagnostic yield of 11.8% (2/17), both of which were exonic-level CNVs with small sizes of 3.03 kb and 5.16 kb beyond the detection thresholds of CMA and ES. Moreover, to the best of our knowledge, we described the first prenatal instance of FGF8 with the manifestation of holoprosencephaly and facial deformities. CONCLUSIONS: Our analysis demonstrated the clinical value of WGS in the diagnosis of the underlying etiology of fetuses with structural abnormalities but failing to diagnose by routine genetic tests. Meanwhile, the novel variants and new fetal manifestations expanded the mutation spectrum and the phenotype spectrum of BBS9 and FGF8. This article is protected by copyright. All rights reserved.

[Efficacy, prognosis and influencing factors of transcatheter arterial embolization in the treatment of neuroendocrine neoplasm liver metastases].

Objective: To evaluate the efficacy of transcatheter arterial embolization (TAE) in the treatment of neuroendocrine neoplasm liver metastases (NENLM), analyze the prognosis and related factors. Methods: Clinical data of NENLM patients treated with TAE in the First Affiliated Hospital of Nanjing Medical University from January 2018 to March 2022 were retrospectively analyzed. Objective response rate (ORR), disease control rate (DCR), and adverse event rate after TAE were evaluated according to the Response Evaluation Criteria In Solid Tumors and the Common Terminology Criteria for Adverse Events. The prognosis was evaluated by median overall survival (mOS) and median progression-free survival (mPFS). The survival curve was plotted by Kaplan-Meier method. Multivariate Cox regression was used to analyze prognostic factors. Results: A total of 39 NENLM patients were included in this study, aged (53.3±10.3) (23-74) years old, including 23 males and 16 females. Among them, 9 cases had functional neuroendocrine neoplasms. There were 31 cases with primary sites locating in the digestive system, 32 cases with WHO G1 and G2 primary sites, 27 cases with abundant blood supply for liver metastases and 13 cases with liver tumor load >50%. Thirty patients received treatment of long-acting somatostatin analogue(SSA). A total of 123 TAE were performed in 39 cases, with an ORR of 38.5% (15/39) and a DCR of 76.9% (30/39). There were no serious adverse events of level 4-5 during the perioperative period. The median follow-up was 38.7 (95%CI: 31.3-46.1) months, with mOS of 37.3(95%CI: 27.0-47.5) months and mPFS of 12.6 (95%CI: 7.1-18.1) months. Multivariate Cox regression analysis found that the combination of long-term SSA treatment was an influencing factor for overall survival of patients (HR=0.207, 95%CI: 0.076-0.567, P=0.002). Conclusions: TAE can effectively reduce the load of liver metastases in patients with NENLM, and the combination of long-term SSA treatment can improve the ovreall survival of patients.

Identification of vulnerable carotid plaque with CT-based radiomics nomogram.

AIM: To develop and validate a radiomics nomogram for identifying high-risk carotid plaques on computed tomography (CT) angiography (CTA). MATERIALS AND METHODS: A total of 280 patients with symptomatic (n=131) and asymptomatic (n=139) carotid plaques were divided into a training set (n=135), validation set (n=58), and external test set (n=87). Radiomic features were extracted from CTA images. A radiomics model was constructed based on selected features and a radiomics score (rad-score) was calculated. A clinical factor model was constructed by demographics and CT findings. A radiomics nomogram combining independent clinical factors and the rad-score was constructed. The diagnostic performance of three models was evaluated and validated by region of characteristic curves. RESULTS: Calcification and maximum plaque thickness were the independent clinical factors. Twenty-four features were used to build the radiomics signature. In the validation set, the nomogram (area under the curve [AUC], 0.977; 95% CI, 0.899-0.999) performed better (p=0.017 and p=0.031) than the clinical factor model (AUC, 0.862; 95% CI, 0.746-0.938) and radiomics signature (AUC, 0.944; 95% CI, 0.850-0.987). In external test set, the nomogram (AUC, 0.952; 95% CI, 0.884-0.987) and radiomics signature (AUC, 0.932; 95% CI, 0.857-0.975) showed better discrimination capability (p=0.002 and p=0.037) than clinical factor model (AUC, 0.818; 95% CI, 0.721-0.892). CONCLUSION: The CT-based nomogram showed satisfactory performance in identification of high-risk plaques in carotid arteries, and it may serve as a potential non-invasive tool to identify carotid plaque vulnerability and risk stratification.

Association of Dietary Quality with Cognitive Function in Chinese Adults Aged 55 Years and Above: A Longitudinal Study.

OBJECTIVES: Diet is an important modifiable factor for brain health and aging. Present study aimed to explore association of dietary quality with cognitive function and poor cognition in middle-aged and older adults participating in the China Health and Nutrition Survey (CHNS). DESIGN: A longitudinal study with a twenty-year follow-up. SETTING AND PARTICIPANTS: Data were drawn from the CHNS 1997, 2000, 2004, 2006, 2015 and 2018. Subjects aged 55 years and more who participated in at least two waves and had completed data on socio-demographics, lifestyle, disease history, anthropometrics, dietary measure and cognitive assessment were eligible in present study. METHODS: Baseline diet were assessed by 3-day 24-hour dietary recalls and used to evaluate diet quality via China Elderly Dietary Guidelines Index 2022 (CDGI 2022-E). Cognitive function was examined using part items of the Telephone Interview for Cognitive Status-modified. Three-level linear mixed effects models and three-level mixed effects logistic regression models were performed to estimate the association between diet quality and cognitive function and odds of poor cognition, respectively. RESULTS: At baseline, 4173 subjects with median age of 63.7 years were recruited. Median of CDGI 2022-E total score was 44.7. Median score of global cognition was 16.0, and the proportion of people with poor cognitive function was 13.9%. Difference in global cognitive score was observed by tertiles of CDGI 2022-E (p<0.05). Significant associations of high diet quality with increment in global cognitive score [ß (95%CI): 0.704 (0.394~1.015)], composite cognitive z score [0.086 (0.045~0.128)] and standardized verbal memory score [0.221 (0.122~0.320)] were observed in total subjects. Consistent associations were also found in those below 65 years at baseline. The likelihood of poor cognition in the highest tertile of CDGI 2022-E decreased by 18% (95%CI: 0.698~0.965) relative to the lowest tertile group in total population. CONCLUSIONS: High diet quality may be beneficial for improving cognitive function and delaying cognitive decline in Chinese middle-aged and older population.

Association of interleukin-6 and CD4+ T cells and two-week prognosis of patients with COVID-19: a predictive role.

OBJECTIVE: The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.

[Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia].

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.