[Fetoscopy for intrauterine diagnosis and treatment of amniotic band syndrome: a clinical analysis of 7 cases and literature review].

Objective: To summarize the clinical value of fetoscopy in the prenatal diagnosis and treatment of amniotic band syndrome (ABS). Methods: A retrospective analysis was conducted on the clinical data of seven ABS fetuses who underwent prenatal fetoscopic intervention at the Third Affiliated Hospital of Zhengzhou University from December 2020 to August 2023. Literatures related to fetoscopic treatment of ABS were searched in databases including China National Knowledge Infrastructure, Wanfang Data, and PubMed. Clinical data were extracted and the characteristics and intervention effects of fetoscopic surgery in the treatment of ABS were summarized. Results: (1) Preoperative evaluation: the gestational age at diagnosis for the seven ABS fetuses was (19.8±4.4) weeks, and the gestational age at fetoscopic intervention was (22.2±2.8) weeks. The indications for fetoscopic intervention included umbilical cord involvement (3 cases), limb amniotic band with circular constriction (2 cases), and unclear visualization of digits (3 cases). (2) Pregnancy outcomes: among the seven ABS fetuses, four cases underwent selective termination of pregnancy due to severe intrauterine limb amputation, and three cases underwent fetoscopic lysis of amniotic bands. Among the latter three cases, one case experienced intrauterine fetal death (IUFD) two weeks after the procedure, and two cases had good postoperative outcomes. (3) Literature review: a total of 40 cases, including 37 cases from 17 articles and three cases from our institution, were included in the analysis. The indications for fetoscopic surgery included limb amniotic band with circular constriction and involvement of the umbilical cord. The success rate of the surgery was 82% (33/40), and 78% (29/37) of the affected limbs retained good functionality. Premature rupture of membranes was the most common complication, with an incidence rate of 48% (16/33). The average interval from the surgery to membrane rupture was (6.1±5.1) weeks, and the average interval from the surgery to delivery was (10.5±4.1) weeks, with an average gestational age at delivery of (33.7±3.6) weeks. The pregnant women were divided into single Trocar group (27 cases) and double Trocar group (13 cases) based on the surgical approach. The success rates in single Trocar group and double Trocar group were 78% (21/27) and 12/13, respectively, and the difference was not statistically significant (χ2=0.474, P=0.491). The gestational age of delivery in the single Trocar group and double Trocar group was (32.7±3.4) and (35.4±3.2) weeks, respectively, and the difference was statistically significant (t=-2.185, P<0.05). There were no statistically significant differences in the success rate of the surgery, incidence of premature rupture of membranes, interval between surgery and membrane rupture, interval between surgery and delivery, and preterm delivery rate between the two groups (all P>0.05). Conclusions: Fetoscopy could be used for prenatal assessment and intrauterine treatment of ABS. Fetoscopic lysis of amniotic bands may be an effective method for treating ABS, which helps preserve limb function and prevent intrauterine limb amputation and IUFD.

[Study on the relationship between hemoglobin glycosylation index and arteriosclerosis- related blood lipids].

Objective: To study the relationship between hemoglobin glycation index (HGI) and blood lipid indices such as low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and plasma atherogenic index (AIP). Methods: This cross-sectional study included 16 049 participants from the Beijing Apple Garden community between December 2011 and August 2012. The subjects were divided into three groups based on the HGI quartile: low (n=5 388), medium (n=5 249), and high (n=5 412). The differences in blood lipid indicators between different HGI groups were compared and multivariate logistic regression model was established to analyze the association between HGI and dyslipidemia. And multivariate logistic regression model was established to analyze the relationship between HGI and blood lipid indicators in different glucose metabolism populations. Results: There were 16 049 participants in all (mean age: 56 years), including 10 452 women (65.1%). They were classified into normal glucose tolerance (9 093 cases), prediabetes (4 524 cases), and diabetes (2 432 cases) based on glucose tolerance status. In the general population, with the increase of HGI, LDL-C, non-HDL-C, and AIP gradually increased (all P values for trends were <0.05), and the proportion of abnormalities increased significantly (χ2=101.40, 42.91, 39.80; all P<0.001). A multivariate logistic regression model was established, which suggested a significant correlation between HGI and LDL-C, non-HDL-C, and AIP (all P<0.05), after adjusting for factors such as age, sex, fasting blood glucose, hypertension, body mass index, smoking, and alcohol consumption. In the overall population, normal glucose tolerance group, and diabetes group, HGI had the highest correlation with non-HDL-C (OR values of 1.325, 1.678, and 1.274, respectively); in the prediabetes group, HGI had a higher correlation with LDL-C (OR value: 1.510); and in different glucose metabolism groups, AIP and HGI were both correlated (OR: 1.208-1.250), but not superior to non-HDL-C and LDL-C. Conclusion: HGI was closely related to LDL-C, non HDL-C, and AIP in the entire population and people with different glucose metabolism, suggesting that HGI may be a predictor of atherosclerotic cardiovascular disease.

[Differential analysis of aqueous humor metabolomics between presenile cataract and senile cataract].

Objective: To explore the differences in metabolites and metabolic pathways in the aqueous humor between patients with presenile cataracts and senile cataracts. Methods: This metabolomic study was conducted at Tianjin Medical University Eye Hospital from August 2020 to September 2022. Eight patients with presenile cataracts (8 eyes) and 8 patients with senile cataracts (9 eyes) were included. Data were collected, including age, gender, preoperative uncorrected visual acuity, intraocular pressure, lens dysfunction index, and axial length. Aqueous humor and anterior capsule tissue samples were obtained during cataract surgery. Metabolites in the aqueous humor were detected using Liquid Chromatography-Mass Spectrometry in a non-targeted approach. The principal component analysis, differential analysis, clustering analysis, and correlation analysis were performed to identify differentially expressed metabolites. These metabolites were ranked based on the fold change (FC). The receiver operating characteristic (ROC) curve analysis and metabolic enrichment analysis were used to identify differential pathways and potential biomarkers for presenile cataracts. Immunohistochemistry was conducted on anterior capsule tissues, and pyruvate levels were measured by colorimetry to validate metabolomic results. Results: Patients with presenile cataracts included 7 males and 1 female, with a mean age of (37.50±4.90) years. Patients with senile cataracts were 7 males and 1 female, with a mean age of (73.44±5.22) years. Except for age, there were no significant differences in baseline data (P>0.05). A total of 347 differential metabolites were identified, 10 of which were potential biomarkers for presenile cataract according to the ROC curve analysis (all P<0.05), including propoxycaine (log2FC=7.26), 2-methyl-2, 3, 4, 5-tetrahydro-1, 5-benzodiazepine-4-ketone (log2FC=6.35), l-pyroglutamic acid (log2FC=-1.72), leanly-proline (log2FC=-0.77), and choline (log2FC=-0.56) in the positive ion mode, and N-phenylacetyl glutamine (log2FC=-1.84), pyruvate (log2FC=1.07), ascorbic acid (log2FC=0.92), pseudouracil nucleoside (log2FC=-0.68), and palmitic acid (log2FC=-0.51) in the negative ion mode. The metabolic enrichment analysis identified 72 differential pathways (32 cationic and 40 anionic), with significant differences in glutathione metabolism, cysteine and methionine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, and the citric acid cycle (P<0.05). The experimental validation showed reduced lactate dehydrogenase and increased pyruvate levels in patients with presenile cataracts (P<0.05). Conclusions: Pyruvate and nine other metabolites may serve as potential biomarkers for presenile cataracts. Pathways involving glutathione metabolism, cysteine and methionine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, and the citric acid cycle are notably dysregulated in patients with presenile cataracts.

The top 100 most cited articles on intramedullary nail fixation from 2018-2022: a bibliometric and visualized analysis.

OBJECTIVE: Intramedullary nails are commonly used for the purposes of internal fixation in the repair of tubular bone fractures, allowing for optimal fixation while minimizing intraoperative bleeding, surgical incision size, and associated stress. These nails are thus often utilized to repair hip and peripheral fractures, femur fractures, tibial fractures, humerus fractures, and clavicle fractures. Recent life expectancy increases, rising economic standards, and technological innovations have led to the application of a wider range of materials and techniques in the context of orthopedic device production, further expanding the clinical indications for intramedullary nailing. Despite the growing importance of this technique, there is currently a lack of any bibliometric or visual analyses that provide a robust overview of recent progress in the intramedullary nailing research space. Accordingly, this study was developed to succinctly and comprehensively summarize the current research status and major hotspots in this field through a bibliometric review of major relevant scientific articles focused on intramedullary nailing published in recent years. MATERIALS AND METHODS: For this analysis, the top 100 most-cited articles focused on intramedullary nails published between 2018 and 2022 were identified through a search of the Web of Science Core Collection database. Countries, institutions, journals, and other specific parameters associated with these articles were then analyzed using tools including CiteSpace, VOS-viewer, Origin, and SCImago Graphica in an effort to more clearly define the latest trends in the intramedullary nail-related research space. RESULTS: The top 3 most-cited articles related to intramedullary nailing over the past five years were "Antibacterial and immunogenic behavior of silver coatings on additively manufactured porous titanium", "Diaphyseal long bone nonunions - types, etiology, economics, and treatment recommendations", and "Epidemiology, treatment, and mortality of trochanteric and subtrochanteric hip fractures: data from the Swedish fracture register", all of which were published in 2018, respectively exhibiting 93, 83, and 81 citations. Of the 100 most-cited intramedullary nailing-related articles, 38, 20, and 12 were respectively published by researchers from the USA, China, and the UK, while research groups from Italy and Spain each published 7 articles. Four of this field's most highly cited articles were published by individuals affiliated with the US-based University of California System and the University System of Ohio. Of the 15 journals that published the largest number of these top 100 articles, the "Injury International Journal of The Care of The Injured" and the "Journal of Orthopaedic Trauma" published 9 manuscripts each, which was more than any other journal, while the "Journal of Orthopaedic Surgery" and the "Journal of Pediatric Orthopaedics" published 7 each. In total, 73 highly cited articles focused on utilizing intramedullary nailing in orthopedic applications. Rozbruch SR from the USA published 3 high-quality articles in this research space, while the Chinese researchers Chang Shi Min, Du Shou Chao, Hou Zhi Yong, and Hu Sun Jun exhibited a total linkage strength of 21 in global interaction analyses. The most common keywords associated with intramedullary nail-related research identified in these analyses included "Hip fracture", "Nonunion", "Limb lengthening", "Proximal humeral fractures", "Additive manufacturing", "Induced membrane", and "Endoprosthetic replacement". Promising areas of potential future research focus may include "Limb reconstruction", "Pediatric deformity", and "Congenital femoral deficiency". CONCLUSIONS: This analysis revealed that the highest volume of high-impact research output focused on intramedullary nailing over the past 5 years has been produced by the USA, followed by China and the UK. The most influential journals in this research space were Injury International Journal of The Care of The Injured and the Journal of Orthopaedic Trauma, while the institutions associated with the most highly cited articles were the University of California System and the University System of Ohio. Intramedullary nailing is commonly utilized to treat intertrochanteric fractures and other tubular bone fractures. In the future, the application of augmented and virtual reality technologies may help shorten the learning curve for orthopedic surgeons and trauma surgeons who are learning intramedullary nailing-related techniques, and the combination of intramedullary nailing with antibacterial drugs, metal alloys, 3D navigation, and sensor devices may help improve patient outcomes.

[Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases].

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

Efficacy and Safety of First-line Therapies for Advanced Unresectable Oesophageal Squamous Cell Cancer: a Systematic Review and Network Meta-analysis.

AIM: To compare the clinical efficacy and safety of first-line treatments for advanced unresectable oesophageal squamous cell cancer. MATERIALS AND METHODS: A systematic review and network meta-analysis was carried out by retrieving and retaining relevant literature from databases. The studies were randomised controlled trials comparing first-line treatments for advanced unresectable oesophageal squamous cell cancer. A Bayesian network meta-analysis was used to assess clinical outcomes. RESULTS: Nine studies including 4499 patients receiving first-line treatments were analysed. For all populations, toripalimab plus chemotherapy tended to provide the best overall survival (hazard ratio 0.58, 95% confidence intervals 0.43-0.78) and sintilimab plus chemotherapy provided the best progression-free survival (0.56, 0.46-0.68). Nivolumab plus chemotherapy presented the best objective response rate (odds ratio 2.45, 1.78-3.42) and camrelizumab plus chemotherapy (0.47, 0.29-0.74) appeared to be the safest. Sintilimab plus chemotherapy (0.55, 0.40-0.75) and nivolumab (0.54, 0.37-0.80) plus chemotherapy had the best overall survival in programmed death ligand 1 (PD-L1) tumour proportion score <1% and ≥1% subgroups. Toripalimab plus chemotherapy (0.61, 0.40-0.93) and pembrolizumab (0.57, 0.43-0.75) were the best in overall survival in combined positive score <10 and ≥10 subgroups, respectively. Toripalimab plus chemotherapy showed the best overall survival in the Asian group; pembrolizumab presented better overall survival in the Asian population than the non-Asian group. CONCLUSION: Most immunotherapy combined with chemotherapy showed superior clinical benefits and sintilimab plus chemotherapy, toripalimab plus chemotherapy and tislelizumab plus chemotherapy had better comprehensive clinical efficacy. PD-L1 expression detection and ethnicity differences are still of great significance and most suitable regimens varied from each subgroup.

[A multicenter study to test the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of clinical application].

Objectives: To verify the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of its clinical application. Methods: A convenience sampling method was used to collect 129 geriatric patients who underwent inguinal hernia surgery from January 2018 to January 2023 in nine hospitals in Liaoning Province. There were 120 males and 9 females, of whom 89 patients were 60 to <75 years old, 33 patients were 75 to <85 years old and 7 patients were ≥85 years old. The 129 patients included 11 elderly patients with inguinal hernia who had recovered from preoperative infection with COVID-19. Statistical methods such as Cronbach's coefficient, Kaiser-Meyer-Olkin test, Bartlett's test, Pearson's correlation analysis, etc. were calculated to verify the reliability indexes such as feasibility, content validity, structural validity, criterion-related validity, internal consistency reliability, and re-test reliability. Taking the 5-item modified frailty index (5-mFI) as the gold standard, the area under the curve was used to analyze the ability of the two scales to predict the occurrence of postoperative acute urinary retention, postoperative delirium, poor incision healing, operative hematoma seroma, and postoperative complications. Results: The frailty assessment scale for elderly patients with inguinal hernia showed good reliability and validity (valid completion rate of 99.2%; item content validity index of 1.000, and the scale content validity index of 1.000; exploratory factor analysis extracted a total of 1 principal component, and factor loadings of each item of 0.565 to 0.873; the AUC for frailty diagnosis using 5-mFI as the gold standard of 0.795 (P<0.01) Cronbach's coefficient of 0.916, retest reliability coefficient of 0.926), it could effectively predict postoperative acute urinary retention, delirium, hematoma seroma in the operative area and total complications (AUC of 0.746, 0.870, 0.806, and 0.738, respectively; all P<0.05), and prediction efficiency was higher than that of 5-mFI (AUC of 0.694, 0.838, 0.626 and 0.641, P<0.05 for delirium only), but both scales were inaccurate in predicting poor incision healing (AUC of 0.519, P=0.913 for the frailty assessment scale and 0.455, P=0.791 for the 5-mFI). Conclusions: The frailty assessment scale for elderly patients with inguinal hernia is reliable and significantly predicts the occurrence of postoperative adverse events in elderly inguinal hernia patients. The scale can also be used for preoperative frailty assessment in elderly patients with inguinal hernia after rehabilitation from COVID-19 infection.

Specific role of NAD+ biosynthesis reduction mediated mitochondrial dysfunction in vascular endothelial injury induced by chronic intermittent hypoxia.

OBJECTIVE: Cardiovascular diseases (CVD) are prevalent among those with obstructive sleep apnea (OSA) and are the leading cause of death in these individuals. However, due to clinical confounders, the mechanism by which OSA induces CVD is still unclear. Previous studies have shown that chronic intermittent hypoxia (CIH) and high cholesterol diet (HCD) induce distinct characteristics of atherosclerotic plaques, highlighting the specific mechanisms involved in CIH-induced vascular endothelial injury. MATERIALS AND METHODS: This study aims to investigate whether nicotinamide adenine dinucleotide (NAD+) biosynthesis reduction-mediated mitochondrial dysfunction is responsible for vascular endothelial injury induced by CIH and to elucidate its specific role in this process. Models were established to stimulate human umbilical vein endothelial cells (HUVECs) with CIH and oxidized low-density lipoprotein (ox-LDL), and the NAD+ biosynthesis-related indicators, such as NAD+ levels and nicotinamide phosphoribosyltransferase (NAMPT) enzyme activity, were measured in this model. Additionally, interventions were performed by supplementing NAD+ levels with nicotinamide mononucleotide (NMN), inhibiting NAD+ synthesis with FK866, and evaluating mitochondrial function, oxidative stress status, vascular constriction and dilation function, and endothelial adhesion function in these models. A comparative study was conducted to assess the effects of these interventions. RESULTS: We found that under CIH conditions, NAMPT enzyme activity was inhibited, leading to a reduction in NAD+ biosynthesis and a decrease in NAD+/NADH ratio. At the same time, CIH caused mitochondrial dysfunction in HUVECs, including a decrease in adenosine triphosphate (ATP) content and mitochondrial membrane potential, as well as the activity of respiratory chain complex I and III, induced an increase in oxidative stress levels in endothelial cells, impaired vascular constriction and dilation function, and significantly increased expression of adhesion factors. The impact of CIH on endothelial cell-related mitochondrial function and endothelial function was restored by supplementing NMN. Although ox-LDL also causes multi-level endothelial injury, it does not involve the NAD+ pathway, as there were no significant changes in the related indicators, and the impaired endothelial function under ox-LDL conditions was not restored by supplementing NMN. CONCLUSIONS: CIH-induced vascular endothelial injury may be associated with NAD+ biosynthesis reduction-mediated mitochondrial dysfunction. Supplementing NAD+ precursors to increase its levels may be a potential intervention to ameliorate CIH-induced vascular endothelial injury, while it does not have a significant effect on endothelial injury caused by ox-LDL.

[Analysis of the relationship between PI-RADS scores and the pathological results of targeted biopsy based on MRI].

Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.

[Application of genetic counseling and preventive surgery in hereditary breast-ovarian cancer syndrome based on a rare family].

Objective: To investigate the genetic, clinical and pathological characteristics of families with hereditary breast-ovarian cancer syndrome (HBOCS) and to explore the implementation of genetic counseling and preventive surgery. Methods: Four siblings with HBOCS in Cancer Hospital/Chinese Academy of Medical Sciences were selected as the study subjects. BRCA gene testing and genetic counseling were performed, family history was traced and family map was drawn. Results: There were 7 cancer patients (Ⅰ 2, Ⅱ 4, Ⅱ 8, Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) in three generations in the family. One patient (Ⅲ 7) had breast cancer and ovarian cancer successively. The first generation (Ⅰ 2) developed cancer at age 60, the second generation (Ⅱ4 and Ⅱ8) developed cancer at 55. The third generation (Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) developed cancer at the age of 42-50 years. Four HBOCS patients were treated in our hospital, and all of them were found to have deleterious BRCA1 mutation. Two had already developed ovarian cancer (Ⅲ 10, Ⅲ 12), while in one case (Ⅲ 11), tubal carcinoma was found during preventive total hysterectomy and pelvic lymph node metastasis was found after the supplementary staging surgery. The other patient without cancer underwent preventive bilateral salpingectomy(Ⅲ 15). Conclusion: The HBOCS family reported in this study is relatively rare, the onset time of tumor was younger generation by generation. It is very important to pay attention to the genetic counseling of ovarian cancer patients and to timely detect the HBOCS families for genetic testing and prophylactic surgery.

[Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma].

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

[Surgical treatment for obstructive hypertrophic cardiomyopathy: a five-year single-center experience of 421 cases].

Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ2=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.

Efficacy and safety of neoadjuvant Folfirinox and Gemcitabine plus Nab-Paclitaxel for borderline resectable and locally advanced pancreatic cancer: a systematic review and meta-analysis.

OBJECTIVE: Multi-agent regimens such as Folfirinox and gemcitabine plus nab-paclitaxel have shown significant improvements compared with single-agent gemcitabine as neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic cancer. However, the efficacy and safety of Folfirinox and GNP as NAC for BRPC and LAPC is still controversial. MATERIALS AND METHODS: The eligible studies including prospective, retrospective, and randomized controlled trial related to Folfirinox and GNP as NAC for patients with BRPC or LAPC up to March 2022 were searched and assessed. Pooled analysis for chemotherapy response rate, resection rate, R0 resection rate, progress free survival, overall survival, and grade 3/4 events of toxicity were performed in the study. RESULTS: Eight studies were included in this meta-analysis. Compared with GNP, Folfirinox had higher resection rate (HR=0.82; 95% CI 0.59-1.14) and R0 resection rate (HR=0.77; 95% CI 0.60-0.97), better PFS (HR=0.78; 95% CI 0.55-1.12) and OS (HR=0.68; 95% CI 0.46-0.99), and without increasing severe toxicity rate (HR=0.95; 95% CI 0.71-1.28). There are no differences in rate of stable disease (HR=1.06; 95% CI 0.92-1.22) and partial/complete regression (HR=0.85; 95% CI 0.59-1.23) between two groups. CONCLUSIONS: Higher resection and R0 resection rate and better PFS and OS results were obtained in Folfirinox group compared with GNP group for patients with BRPC and LAPC. There was no increased severe toxicity rate for Folfirinox compared with GNP.

[Value of albumin RNAscope in situ hybridization in diagnosis and differential diagnosis of hepatocellular carcinoma].

Objective: To investigate the utility of albumin RNAscope in situ hybridization in the diagnosis and differential diagnosis of hepatocellular carcinoma and its mimics. Methods: One hundred and fifty-two cases of hepatocellular carcinoma and its mimics and 33 cases of normal tissue were selected from the pathology database of the Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019. Tissue microarrays were constructed and RNAscope in situ hybridization was performed to detect the expression of albumin mRNA. Results: No albumin mRNA expression was detected in normal tissues except for the liver. All hepatocellular carcinoma regardless of its degree of differentiation and primary or metastatic nature had detectable albumin mRNA, with strong and diffuse staining in 90.7% (49/54) of cases. While the positive rate of HepPar-1, Arg-1 or one of them by immunohistochemistry was 87.0% (47/54), 85.2% (46/54) and 92.6% (50/54) respectively. The positive rates of albumin mRNA in intrahepatic cholangiocarcinoma and biphenotypic hepatocellular carcinoma were 7/15 and 9/10, respectively. The former showed focal or heterogeneous staining, while the latter showed strong and diffuse staining. The positive rate of hepatoid adenocarcinoma was 8/19, and the albumin expression could be diffuse or focal. Sporadic cases of poorly differentiated gastric adenocarcinoma and metastatic colon adenocarcinoma showed focal staining of albumin mRNA. Conclusions: Detection of albumin mRNA by RNAscope in situ hybridization is of great value for the diagnosis and differential diagnosis of HCC, and the sensitivity may be improved by combining with HepPar-1 and Arg-1. It also offers different diagnostic clues according to different expression patterns.

[Pyroptosis of lens epithelial cells in diabetic cataract].

Objective: To investigate the possible role of pyroptosis of lens epithelial cells (LECs) in the occurrence of diabetic cataract. Methods: Experimental research. A total of 70 cataract lens anterior capsule and aqueous humor samples were obtained from 70 eyes (70 patients) with cataracts in the operation room of Tianjin Medical University Eye Hospital between March 2020 and November 2020. Patients were divided into the non-diabetic and diabetic groups, with 35 patients (35 eyes) in each group. The expressions of Nod like receptor protein 3 (NLRP3), cysteine-aspartic proteases 1 (caspase-1) and Gasdermin D protein (GSDMD) in the lens anterior capsule were detected by Western blotting, real-time quantitative PCR and immunohistochemical staining. Interleukin (IL)-1ß and IL-18 inaqueous humor were detected by enzyme-linked immunosorbent assay (ELISA). The independent sample t-test was used for statistical analysis. Results: The age was (70±9) years in the diabetic group and (71±8) years in the non-diabetic group. There was no significant difference in age and gender distribution between the two groups (both P>0.05). Western blotting analysis showed that the expression levels of NLRP3, caspase-1 and GSDMD protein in the LECs of anterior capsule were 1.11±0.06, 0.95±0.04 and 0.39±0.03 in the diabetic group, significantly higher than those of the non-diabetic group (0.81±0.04, 0.33±0.11 and 0.16±0.04; t=4.38, 5.36, 4.63; all P<0.05). Real-time quantitative PCR showed that the levels of NLRP3, caspase-1 and GSDMD mRNA in the LECs of anterior capsule were 1.98±0.07, 54.36±4.88 and 6.98±1.18 in the diabetic group, significantly higher than those of the non-diabetic group (1.38±0.16, 15.31±1.51 and 2.41±0.95; t=3.49, 7.64, 3.00, all P<0.05). Immunohistochemical staining showed that the average gray values of NLRP3, caspase-1 and GSDMD in the diabetic group were higher than those of the non-diabetic group (all P˂0.01). ELISA showed that the levels of IL-1ß and IL-18 in the aqueous humor were (4.178±0.028) fg/L and (20.983±0.018) fg/L in the diabetic group, significantly higher than those of the non-diabetic group [(4.063±0.017) fg/L and (20.509±0.073) fg/L; t=20.63, 37.21; both P˂0.01]. Conclusion: Caspase-1-mediated pyroptosis of LECs and the release of inflammatory mediators induced by pyroptosis may be involved in the occurrence and development of diabetic cataract.

[Clinical analysis of chronic eosinophilic pneumonia in 9 cases].

Objective: To investigate the clinical features, treatment and prognosis of chronic eosinophilic pneumonia. Methods: Nine patients with chronic eosinophilic pneumonia diagnosed in Shandong Provincial Qianfoshan Hospital from January 2014 to December 2020 were enrolled and followed up. The data of clinically proven chronic eosinophilic pneumonia were reviewed. Results: The 9 cases included one male and eight females, aged from 16 to 71 years (median 47 years). Among them, 5 cases were complicated with asthma, 1 case was complicated with allergic rhinitis, and 1 case had an allergic history of pollen. All the patients had cough, expectoration, chest tightness and wheezing, and a few had fatigue (3/9), fever (1/9) and chest pain (1/9). Single or multiple patchy high-density shadows (9/9), mediastinal lymphadenopathy (7/9), air bronchogram (2/9), and reticular shadow (1/9) were observed in chest CT. Peripheral eosinophils (EOS) and serum total IgE increased to varying degrees in the 9 patients. Meanwhile, the bronchoscopy of 5 cases showed elevated percentage of eosinophils in alveolar lavage fluid, and the lung biopsy of remaining 4 cases showed EOS infiltration in lung alveolar and interstitium. After receiving glucocorticoid therapy for 0.5 to 1 month, the clinical symptoms of all 9 patients had been improved and lung lesions on CT scans had been obviously absorbed. Four cases relapsed during follow-up. Conclusions: For patients especially women who have a history of allergy, elevated blood eosinophils and serum total IgE with pulmonary high-density shadow or consolidation, chronic eosinophilic pneumonia should be considered, and bronchoscopy or percutaneous lung biopsy is indicated for a definite diagnosis. Glucocorticoid therapy is effective, but the rate of recurrence is high.