[Scientific, transparent and applicable rankings of Chinese pathological guidelines and consensus published in the medical journals in 2022].

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.

[A successfully treated case of respiratory failure caused by eating Nassariidaes].

Food poisoning caused by Nassariidaes has occurred frequently in coastal areas of China, especially in summer and autumn. Nassariidaes poisoning can be manifested as lip and tongue paralysis, dizziness, headache, nausea and vomiting, arrhythmia and even respiratory failure. We admitted a case of respiratory failure caused by eating Nassariidaes. After timely respiratory support, hemoperfusion and other active treatment, the patient was recovered and was discharged. This paper summarized clinical characteristics and treatment of Nassariidaes poisoning, in order to provide reference for clinical diagnosis and treatment of similar cases.

[Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF)].

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

[Relationship between blood uric acid levels and body composition in patients with polycystic ovary syndrome].

Objective: To analyze the difference in blood uric acid levels between patients with polycystic ovary syndrome (PCOS) and healthy women of childbearing age, and to investigate the correlation between body composition and blood uric acid levels. Methods: A total of 153 eligible childbearing age patients with PCOS treated at Tianjin Medical University General Hospital from January 2018 to March 2022 were selected, and 153 healthy women with normal menstruation were selected as the control group. Fasting blood uric acid levels were measured by venous blood test, and body composition was measured by a body composition analyzer. Group comparisons were made to analyze the correlation between body composition and blood uric acid levels. Results: The incidence of hyperuricemia was higher in patients with PCOS than that in the control group [30.1% (46/153) vs 2.0% (3/153)], with a statistically significant difference (χ2=44.429, P<0.001). Blood uric acid level was also significantly higher in patients with PCOS than that in the control group [(371±98) vs (265±67) µmol/L; t=11.170, P<0.001]. Among PCOS patients, there were statistically significant differences in weight, body mass index (BMI), body fat mass, skeletal muscle mass, percent body fat, lean body weight, fat mass/lean body weight, percent skeletal muscle, and visceral fat level between the hyperuricemia group and the normal blood uric acid group (all P<0.001), but no significant difference was observed in waist-hip ratio (P=0.348). The following body composition indicators: weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, visceral fat level, lean body weight, and fat mass/lean body weight in all subjects, the PCOS patients and the control group, were positively correlated with blood uric acid levels (all P<0.01). The blood uric acid level in PCOS obese patients was higher than that in non-obese PCOS patients, and the difference was statistically significant [(425±83) vs (336±91) µmol/L; t=6.133, P<0.001]. The blood uric acid level in central obesity PCOS patients was also higher than that in non-central obesity PCOS patients [(385±95) vs (299±79) µmol/L], the difference was statistically significant (t=4.261, P<0.001). The blood uric acid level in normal-weight obese PCOS patients was higher than that in normal-weight non-obese PCOS patients [(333±73) vs (277±54) µmol/L], and the difference was statistically significant (t=2.848, P=0.006). Blood uric acid levels in normal-weight [(315±74) vs (255±67) µmol/L], overweight [(362±102) vs (276±57) µmol/L], and obese PCOS patients [(425±83) vs (303±74) µmol/L] were all higher than those in the corresponding control groups, with statistically significant differences (all P<0.001). Conclusions: PCOS patients have a higher incidence of hyperuricemia than healthy women of childbearing age. Blood uric acid levels are closely correlated with body composition indicators, such as weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, and visceral fat level. Body composition analysis of women with PCOS could help identify potentially obese people more accurately and carry out individualized treatment, thereby reducing the risk of metabolic abnormalities.

[Establishment and evaluation of a method for phages enrichment by ferric trichloride-polyvinylidene fluoride membrane filter].

Objective: To establish and evaluate a method of enriching bacteriophages in natural water based on ferric trichloride-polyvinylidene fluoride (FeCl3-PVDF)membrane filter. Methods: Based on the principle of flocculation concentration, the method of recovering bacteriophage from water sample was established by using iron ion flocculation combined with membrane filter. The titer of phage was determined by Agar double layer method. The recovery efficiency of phage was detected by phage fluorescence staining and real-time fluorescence PCR reaction. Water samples from different sources were collected for simulation experiment to evaluate the enrichment effect. At the same time, the sewage discharged from hospitals was taken as the actual water sample, and the common clinical drug-resistant bacteria were used as the host indicator bacteria to further analyze the enrichment effect of FeCl3-PVDF membrane filter rapid enrichment method on the bacteriophage in natural water samples. Results: The method of enrichment of bacteriophages in natural water by iron ion concentration 50 mg/L and PVDF membrane filter was established. The recovery rate of this method for bacteriophage was 93%-100%. Under the multi-functional microscope, it was found that the bacteriophage of the enriched water sample increased significantly and the fluorescence value of the enriched water sample determined by the enzyme labeling instrument was about 13 times as high as that before enrichment. After concentration of the actual water samples from the hospital drainage, the positive rate of bacteriophage isolation in the concentrated group and the non-concentrated group was 23% and 4%, and the fluorescence value in the concentrated group was 2-24 times as high as that of the non-concentrated group. Conclusion: The method of FeCl3-PVDF membrane filter is a simple, efficient and rapid method for enriching bacteriophages in different water samples.

[Study on the distribution pattern of allergen sIgE in patients with respiratory allergic diseases in a hospital in Shanxi Province].

To explore the allergen sensitization status of patients with respiratory allergic diseases in Shanxi Province, and to provide a basis for the diagnosis, treatment and prevention of allergic diseases. It is a cross-sectional study, a total of 1 680 patients with allergic rhinitis and/or asthma diagnosed at the Department of Allergic Reaction of Shanxi Bethune Hospital from July 2021 to June 2023 who underwent allergen sIgE testing and/or skin prick test were retrospectively enrolled.There were 772 males and 908 females.The age range was 3 to 88 years. The median age was 35 years.There were 108 cases in the child group (≤12 years old), 102 cases in the adolescent group (13-17 years old), 819 cases in the youth group (18-40 years old), 498 cases in the middle-aged group (41-65 years old), and 153 cases in the elderly group (>65 years old). There were 333 cases in the allergic rhinitis group, 827 cases in the allergic asthma group, and 520 cases in the allergic rhinitis with asthma group. There were 1 254 urban patients and 426 rural patients.There were 253 cases in the northern Shanxi region, 1 195 cases in the central Shanxi region, and 232 cases in the southern Shanxi region. Statistical analyses were performed using the χ 2 test or Fisher's exact probability method to compare the differences in allergen sIgE positivity rates by sex, age, disease, living environment, and geography. The results showed that 1 027 patients (61.1%) were positive for at least one allergen sIgE, with Artemisia having the highest rate of positivity (603/1 680, 35.9%), followed by ragweed (302/1 680, 18.0%) and dust mite combinations (245/1 680, 14.6%). The number of individuals with single-allergen sIgE positivity was 357 (357/1 027, 34.8%), with the highest number of single-allergen sIgE positive results associated with Artemisia (114/357, 31.9%). The number of multiple-allergen sIgE positive results was 670 cases (670/1 027, 65.2%), with the highest number of patients having 2 allergen sIgE positive results (243/670, 36.3%). The overall positivity rate for allergen sIgE was significantly higher among males than among females (65.7% vs. 57.3%, χ2=12.405, P<0.001). Overall positivity for inhalant allergen sIgE was higher in the child and adolescent groups (88.0% vs. 88.2% vs. 59.8% vs. 40.2% vs. 19.0%, χ2=223.372, P<0.001), and food allergen sIgE positivity was highest in the child group (54.6% vs. 36.3% vs. 26.0% vs. 18.9% vs. 21.6%,χ2=66.383,P<0.001). The sIgE positivity rate of inhalant allergens was significantly higher in the allergic rhinitis group and the allergic rhinitis with asthma group than in the allergic asthma group, except for cockroaches and molds (P<0.05). The overall positive rate of allergen sIgE was significantly higher among urban patients than among rural patients (66.2% vs. 46.2%, χ2=53.230, P<0.001). The difference in the overall positive rate of allergen sIgE among patients from different regions was not statistically significant (56.1% vs. 62.0% vs. 62.1%, χ2=3.140, P=0.208). The sIgE positivity of dust mite combinations was significantly higher in the central Shanxi region and the southern Shanxi region than in the northern Shanxi region (15.5% vs. 18.1% vs. 7.1%,χ2=14.411, P=0.001). In conclusion, artemisia was the most important sensitizer for respiratory allergic diseases in Shanxi Province. The types of allergens and positivity rates were different for different sexes, ages, diseases, living environments, and regions. Therefore, patients with allergic diseases should be tested for allergens to help with the diagnosis, treatment and prevention of allergic diseases.

[Fibroma of tendon sheath: a clinicopathological and genetic analysis of 134 cases].

Objective: To investigate the clinicopathological features, immunophenotypes and molecular genetics of fibroma of tendon sheath (FTS). Methods: One hundred and thirty-four cases of FTS or tenosynovial fibroma diagnosed in the Department of Pathology, West China Hospital, Sichuan University, Chengdu, China from January 2008 to April 2019 were selected. The clinical and histologic features of these cases were retrospectively reviewed. Immunohistochemistry, fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR) were performed on the above cases. Results: There were a total of 134 cases of FTS, including 67 males and 67 females. The patients' median age was 38 years (ranged from 2 to 85 years). The median tumor size was 1.8 cm (ranged from 0.1 to 6.8 cm). The most common site was the upper extremity (76/134, 57%). Follow-up data was available in 28 cases and there was no detectable recurrence. Classic FTS (114 cases) were well-defined and hypocellular. A few spindle-shaped fibroblasts were scattered in the dense collagenous sclerotic stroma. Characteristically elongated slit-like spaces or thin-walled vessels were observed. Most of cellular FTSs (20 cases) were well-defined and the area with increased cellularity of the spindle cells coexisted with classic FTS. There were occasional mitotic figures, but no atypical mitotic figures. Immunohistochemistry was performed in 8 cases of classic FTS and most cases were positive for SMA (5/8). Immunohistochemistry was also performed in 13 cases of cellular FTS and showed 100% positive rate for SMA. FISH was conducted on 20 cases of cellular FTS and 32 cases of classical FTS. USP6 gene rearrangement was found in 11/20 of cellular FTS. Among 12 cases of CFTS with nodular fasciitis (NF)-like morphological feature, 7 cases showed USP6 gene rearrangement. The rearrangement proportion of USP6 gene in cellular FTS without NF-like morphological features was 4/8. By contrast, 3% (1/32) of the classic FTS showed USP6 gene rearrangement. RT-PCR was performed in those cases with detected USP6 gene rearrangement and sufficient tissue samples for RT-PCR. The MYH9-USP6 fusion gene was detected in 1 case (1/8) of the cellular FTSs, while no target fusion partner was detected in the classic FTS. Conclusions: FTS is a relatively rare benign fibroblastic or myofibroblastic tumor. Our study and recent literature find that some of the classic FTS also show USP6 gene rearrangements, suggesting that classical FTS and cellular FTS are likely to be at different stages of the same disease (spectrum). FISH for USP6 gene rearrangement may be used as an important auxiliary diagnostic tool in distinguishing FTS from other tumors.

[Cryptic COL1A1-PDGFB fusion in dermatofibrosarcoma protuberans: a clinicopathological and genetic analysis].

Objective: To investigate the clinicopathological and cytogenetic features of cryptic COL1A1-PDGFB fusion dermatofibrosarcoma protuberans (CC-DFSP). Methods: Three cases of CC-DFSP diagnosed in West China Hospital, Sichuan University, Chengdu, China from January 2021 to September 2021 were studied. Immunohistochemistry for CD34 and other markers, fluorescence in situ hybridization (FISH) for PDGFB, COL1A1-PDGFB and COL1A1, next-generation sequencing (NGS), reverse-transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing were performed. Results: There were three cases of CC-DFSP, including two females and one male. The patients were 29, 44 and 32 years old, respectively. The sites were abdominal wall, caruncle and scapula. Microscopically, they were poorly circumscribed. The spindle cells of the tumors infiltrated into the whole dermis or subcutaneous tissues, typically arranging in a storiform pattern. Immunohistochemically, the neoplastic cells exhibited diffuse CD34 expression, but were negative for S-100, SMA, and Myogenin. Loss of H3K27me3 was not observed in the tumor cells. The Ki-67 index was 10%-15%. The 3 cases were all negative for PDGFB rearrangement and COL1A1-PDGFB fusion, whereas showing unbalanced rearrangement for COL1A1. Case 1 showed a COL1A1 (exon 31)-PDGFB (exon 2) fusion using NGS, which was further validated through RT-PCR and Sanger sequencing. All patients underwent extended surgical resection. Except for case 3 with recurrence 2 years after surgical resection, the other 2 cases showed no recurrence or metastasis during the follow-up. Conclusions: FISH has shown its validity for detecting PDGFB rearrangement and COL1A1-PDGFB fusion and widely applied in clinical detection. However, for cases with negative routine FISH screening that were highly suspicious for DFSPs, supplementary NGS or at least COL1A1 break-apart FISH screening could be helpful to identify cryptic COL1A1-PDGFB fusions or other variant fusions.

[Primary central nervous system T-cell lymphoma in children and adolescents: a clinicopathological analysis of five cases].

Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.

[Associations between various lipid components and premature myocardial infarction: a cross-sectional study].

Objective: Hyperlipidemia is closely related to premature acute myocardial infarction (AMI). The present study was performed to explore the correlation between various blood lipid components and the risk of premature AMI. Methods: This is a cross-sectional retrospective study. Consecutive patients with acute ST-segment elevation myocardial infarction (STEMI), who completed coronary angiography from October 1, 2020 to September 30, 2022 in our hospital, were enrolled and divided into premature AMI group (male<55 years old, female<65 years old) and late-onset AMI group. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, lipoprotein (a) (Lp (a)), apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA-1), non-HDL-C/HDL-C and ApoB/ApoA-1 were analyzed. The correlation between the above blood lipid indexes and premature AMI was analyzed and compared by logistic regression, restricted cubic spline and receiver operating characteristic curve (ROC). Results: A total of 1 626 patients with STEMI were enrolled in this study, including 409 patients with premature AMI and 1 217 patients with late-onset AMI. Logistic regression analysis showed that the risk of premature AMI increased significantly with the increase of TG, non-HDL-C/HDL-C, non-HDL-C, ApoB/ApoA-1, TC and ApoB quintiles; while LDL-C, ApoA-1 and Lp (a) had no significant correlation with premature AMI. The restricted cubic spline graph showed that except Lp (a), LDL-C, ApoA-1 and ApoB/ApoA-1, other blood lipid indicators were significantly correlated with premature AMI. The ROC curve showed that TG and non-HDL-C/HDL-C had better predictive value for premature AMI. Inconsistency analysis found that the incidence and risk of premature AMI were the highest in patients with high TG and high non-HDL-C/HDL-C. Conclusion: TG, non-HDL-C/HDL-C and other blood lipid indexes are significantly increased in patients with premature AMI, among which TG is the parameter, most closely related to premature AMI, and future studies are needed to explore the impact of controlling TG on incidence of premature AMI.

[Efficacy of dienogest versus gonadotropin-releasing hormone agonist combined with dienogest sequential therapy in the treatment of adenomyosis].

Objective: To investigate the efficacy and safety of dienogest (DNG) alone and gonadotropin-releasing hormone agonist (GnRH-a) combined with DNG sequential treatment to adenomyosis. Methods: The clinical data of 110 patients with adenomyosis attending the First Affiliated Hospital of Nanjing Medical University from December 2019 to March 2022 were retrospectively analyzed, including 40 patients treated with DNG (2 mg/day) alone (DNG group) and 70 patients treated with sequential DNG (2 mg/day) after 3-6 injections of GnRH-a (GnRH-a+DNG group). The clinical data before and after treatment were compared between the two groups. Results: (1) The dysmenorrhea visual analogue scale (VAS) scores, cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) levels at different time periods after treatment were significantly lower than before treatment in both groups (median before treatment: DNG group 70.0 mm, 68.55 kU/L, 22.45 kU/L respectively, GnRH-a+DNG group 80.0 mm, 151.50 kU/L, 20.44 kU/L respectively; all P<0.001). (2) The hemoglobin (Hb) levels of patients in both groups at different time periods after treatment were significantly higher than those before treatment (median: DNG group 102.00 g/L, GnRH-a+DNG group 94.00 g/L; all P<0.001). (3) Treatment with DNG alone did not have a significant effect on uterine volume in patients of DNG group (P>0.05), and uterine volume decreased significantly in the 15th-24th months of GnRH-a+DNG group compared with that before treatment (median: 167.76 vs 227.77 cm3; P<0.05). (4) There were no significant differences in hepatic and renal function and coagulation indexes between the two groups before and after treatment (all P>0.05), and no significant abnormal lesions were observed in breast tissue during the follow-up period. (5) The incidence of amenorrhea of GnRH-a+DNG group was higher than that of DNG group, and the incidences of irregular spotting bleeding and breakthrough hemorrhage were lower than those in DNG group. Conclusions: Whether DNG is used alone or in combination with GnRH-a in sequence, it could significantly relieve dysmenorrhea symptoms, improve the level of Hb, reduce the levels of CA125 and CA19-9 in patients with adenomyosis, with no adverse effects on coagulation and hepatic or renal function. GnRH-a sequential DNG therapy is superior to DNG alone in improving uterine bleeding patterns and controlling the growth of uterine volume in patients with adenomyosis.

[Changes of coagulation function in patients with adenomyosis].

Objective: To explore the different coagulation state in patients with adenomyosis and its clinical significance. Methods: Clinical data of the patients admitted to the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2021 were retrospectively analyzed. (1) Differential coagulation state between 25 healthy women and 25 patients with adenomyosis were compared during menstrual and non-menstrual periods. (2) The coagulation indexes of 145 patients with adenomyosis (observation group 1) and 129 patients with cervical intraepithelial neoplasia grade Ⅲ (control group 1) who underwent hysterectomy in non-menstrual period were compared. (3) The coagulation indexes of 154 patients with adenomyosis (observation group 2) and 147 women without myometrial lesions (control group 2) who underwent endometrial curettage during uterine bleeding period were compared. (4) Correlations of coagulation index with cancer antigen 125 (CA125), cancer antigen 19-9 (CA19-9) and uterine volume in patients with adenomyosis were analyzed. Results: (1) The coagulation state of each health women during the menstrual and non-menstrual period showed no significant differences (all P>0.05). For the 25 patients with adenomyosis, fibrinogen [FIB; 2.61 g/L(2.50-3.10 g/L)] and D-dimer [0.60 mg/L (0.40-1.00 mg/L)] in the menstrual period were significantly higher than those in the non-menstrual period [2.25 g/L (1.90-2.70 g/L) and 0.27 mg/L (0.20-0.40 mg/L), respectively; both P<0.01], while thrombin time [TT; 16.70 s (16.10-17.40 s)] in the menstrual period was significantly lower than that in the non-menstrual period [17.95 s (17.20-18.40 s); P<0.01]. (2) In the non-bleeding period, D-dimer [0.26 mg/L (0.20-0.40 mg/L)] and platelet count [257.0×109/L (212.0×109/L-308.5×109/L)] of observation group 1 were significantly higher than those of control group 1 (all P<0.01). Besides, FIB (r=0.237, P=0.004) and D-dimer (r=0.373, P<0.001) were positively correlated with CA125, while prothrombin time (PT; r=-0.208, P=0.012) and internationalized normalized ratio of plasma prothrombin time (PT-INR; r=-0.201, P=0.015) were negatively correlated with CA19-9. (3) In the bleeding period, PT [10.70 s (10.10-11.20 s)] and PT-INR [0.93 (0.90-1.00)] of observation group 2 were significantly lower than those of control group 2 (all P<0.01), while D-dimer [0.41 mg/L (0.20-0.80 mg/L)] was significantly higher than that in the control group 2 (P<0.001). Furthermore, FIB (r=0.252, P=0.038) and D-dimer (r=0.321, P=0.008) were positively correlated with uterine volume, while activated partial thromboplastin time (APTT; r=-0.190, P=0.018) and TT (r=-0.304, P=0.012) were negatively correlated with uterine volume. (4) During non-menstrual period and uterine bleeding period, APTT and TT in patients of observation group 1 and 2 combined with anemia were significantly lower than those of non-anemia patients (all P<0.05). Conclusion: Patients with adenomyosis have a tendency to hypercoagulability in both the uterine bleeding and non-bleeding periods, which may be related to enlarged uterine volume, increased serum CA125 and anemia.

[Spindle cell hemangioma: a clinicopathological and molecular analysis of eight cases].

Objective: To investigate the clinicopathological and genetic characteristics of spindle cell hemangioma (SCH). Methods: The clinical, morphological and immunohistochemical features of 8 SCHs diagnosed from January 2013 to September 2021 in West China Hospital, Sichuan University, Chengdu, China were retrospectively analyzed. Hotspot mutations for IDH1 codon 132 and IDH2 codon 172 were tested in 4 SCHs and 29 other non-SCH lesions using Sanger sequencing. Results: The 8 cases occurred in patients with a wide age range, from neonate to 46 years (mean 28 years, median 32 years). Both genders were equally affected. The course of the disease spanned from half a year to 31 years. Two SCHs were recurrent tumors. All tumors involved the distal extremities (4 of foot, 2 of ankle and 2 of hand). Six cases were presented as a single lesion and 2 cases as multiple lesions. The tumor diameters were 1-5 cm. All the 8 SCHs were typically composed of cavernous vascular space and solid components consisting of slit-like vessels, spindle cells and epithelioid endothelial cells which often exhibited cytoplasmic vacuolation. These two alternating components and the vacuolated epithelioid endothelial cells were the distinctive diagnostic clues for SCH. Vascular endothelial cells including epithelioid cells in the solid areas expressed CD31 (8/8), ERG (4/4), CD34 (5/8) and D2-40 (2/3). The spindle cells expressed SMA (8/8). Neither endothelial cells nor spindle cells expressed HHV8 (0/7), Desmin (0/5) or S-100 (0/3). Mutations were revealed in 2 SCHs, with IDH1 mutation (p.R132C) and IDH2 mutation (p.R172G), respectively. The IDH1/2 gene hotspot mutations were not found in the remaining 2 SCHs or the other 29 non-SCH lesions. Simple excisions were performed for 7 cases, and partial resection for 1 case. Follow-up information was obtained in 6 cases, with follow-up time ranging from 5 to 90 months (average, 46 months). No metastasis occurred in the 6 cases. No recurrence occurred in cases treated with simple excision. The residual lesions of the patient who received partial resection were stable. Conclusions: SCH is rare and should be differentiated from a variety of benign and malignant vascular lesions. An accurate diagnosis of SCH is clinically important and can be achieved by combining clinical information and typical pathological presentation. IDH1/2 gene hotspot mutations are specific to SCH in vascular lesions. Genetic detection is helpful in the diagnosis of challenging cases.

[Diagnostic value of MDM2 RNA in situ hybridization in atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma].

Objective: To investigate the value of MDM2 RNA in situ hybridization (RNA-ISH) in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Methods: A total of 26 ALT/WDL/DDLs diagnosed from March 2017 to May 2019 in West China Hospital, Sichuan University, Chengdu, China and 18 control cases were included. MDM2 RNA-ISH was performed on all samples and compared with the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) regarding their performance in detecting MDM2. Results: All samples were detected successfully using the three methods. Among 26 ALT/WDL/DDLs, all cases showed MDM2 amplification and positivity for MDM2 RNA-ISH (26/26, 100%). Twenty-four (24/26, 92.3%) of the 26 tested cases were positive for MDM2 IHC while two of them were negative. Eighteen control cases were all negative for MDM2 FISH and RNA-ISH, and 15 (15/18) cases were negative for MDM2 IHC. The sensitivity and specificity of RNA-ISH were both 100%, and those of MDM2 IHC were 92.3% and 83.3%, respectively. Diffuse staining was identified in all MDM2 RNA-ISH positive ALT/WDL/DDLs, but identified in only 8/24 (33.3%) of the MDM2 IHC positive cases. Among the 11 ALT/WDL/DDL samples evaluated on tissue microarray, the positive rate of MDM2 RNA-ISH was 100% with diffuse staining in all cases. The positive rate of MDM2 IHC was 9/11 while only 1 of the 9 cases showed diffuse staining. The result of MDM2 RNA-ISH was identical to that of MDM2 FISH and was overall consistent with that of MDM2 IHC (Kappa=0.763, P<0.001). Conclusions: In ALT/WDL/DDLs, results of MDM2 RNA-ISH are highly consistent with those of FISH. MDM2 RNA-ISH is more sensitive and more specific and has more diffuse positive signals than the IHC. The findings indicate that MDM2 RNA-ISH is highly valuable for the diagnosis and differential diagnosis of ALT/WDL/DDLs.

[Retrospective analysis of clinical characteristics of patients with metabolic-associated fatty liver disease at high and low altitude areas].

Objective: To explore differences in clinical characteristics and hemoglobin levels between different age groups in patients with metabolic-associated fatty liver disease (MAFLD) at high and low altitude areas, so as to provide a basis for further research on the effect of chronic hypoxia on MAFLD. Methods: Liver function indexes, non-invasive fibrosis indexes, metabolic indexes, and routine blood test of 1 458 (Xining area of Qinghai province) and 1 633 cases (Huzhou area, Zhejiang province) with MAFLD who underwent physical examination were retrospectively analyzed. The total population of the two places were compared and analyzed with the hemoglobin reference limit of 180 g/L. The population of Xining was divided into high and low hemoglobin groups for comparative analysis. The population of the two places was divided into five groups according to age stratification (≤30 years old, 31-40 years old, 41-50 years old, 51-60 years old, ≥61 years old). After multivariate adjustment, the characteristics of high and low hemoglobin groups and MAFLD were compared between the two groups. Statistical analysis was performed with t-test or χ2 test. Results: The detected indexes values observed were higher in Xining than Huzhou area population [fibrosis indexes (FIB4, 1.08±0.02 vs. 1.19±0.02), erythrocyte (5.14±0.13 vs. 5.30±0.13), hemoglobin (156.82±0.37 vs. 164.19± 0.39), alanine aminotransferase (ALT, 33.70±0.66 vs. 43.68±0.70), aspartate aminotransferase (AST, 24.34±0.28 vs. 29.23±0.30), γ-glutamyltransferase (42.40±1.02 vs. 51.82±1.53), alkaline phosphatase (77.92±0.56 vs. 84.63±0.85), triglyceride (TG, 2.07±0.04 vs. 2.74±0.05), uric acid (UA, 383.42±2.15 vs. 406.44±2.36)]. The detected indexes values observed were higher in Huzhou than Xining area population [platelet count (220.54±1.32 vs. 181.62±1.40), total cholesterol (TC, 5.10±0.02 vs. 5.04±0.03), fasting blood glucose (FBG, 5.67±0.04 vs. 5.29±0.04)]. The differences were statistically significant (P<0.01). Xining population UA and body mass index were increased in high hemoglobin group than low hemoglobin group, and the other parameters difference were not statistically significant. After the population in Xining was grouped by age, high and low FIB4, ALT, and AST and UA levels were detected in the age group of 31-40 and 51-60 years old, >61 years old, 31-40 years old, and the difference between hemoglobin groups were statistically significant (P<0.01). Conclusion: Patients with MAFLD are more likely to develop fibrosis, liver function impairment, metabolic disorders and so on under high-altitude hypoxic environment. Additionally, there is certain correlation with disease severity and age changes, suggesting that chronic hypoxia can accelerate MAFLD progression.

[Risk factors of perinatal complications in patients with pulmonary hypertension underwent cesarean section in 4 Chinese centers].

Objective: To identify the risk factors related to perinatal complications in patients with pulmonary hypertension underwent cesarean section. Methods: We retrospectively analyzed the medical records of all pregnant women with pulmonary hypertension hospitalized in 4 different hospitals in Shandong province and underwent cesarean section between May 2010 and May 2020. Patients were divided into perinatal complication group and control group according to the presence or absence of perinatal complications. Perinatal complications included aggravated heart function, new onset arrythmias, sudden cardiac arrest, all-cause death within 42 days post cesarean section, postpartum bleeding and thrombotic events. Risk factors of perinatal complications were analyzed. Results: A total of 167 patients (47 cases in the perinatal complication group and 120 cases in the control group) were included in this study. The average age of this cohort was 28(24, 32) years, and 75(44.9%) patients suffered newly diagnosed pulmonary hypertension during pregnancy. The main cause of pulmonary hypertension was congenital heart disease (137(82.0%)). Age, pregnant weeks, percent of primipara, intra-cardiac shunt, and receiving targeted medication therapy, cardiac dimensions were similar between the two groups. A total of 62 complications were recorded in the complication group including 28 cases of aggravated heart function, 4 cases of new onset arrythmias, 2 cases of cardiac arrest, 11 cases of bleeding or thrombotic events and 17 patients were dead. Prevalence of idiopathic pulmonary hypertension and general anesthesia was significantly higher, functional capacity was significantly lower in perinatal complication group than in control group (all P<0.05). The estimated systolic pulmonary artery pressure, serum N-terminal pro-B type natriuretic peptide and total bilirubin (TBIL) levels were significantly higher in perinatal complication group than in control group (all P<0.05). Logistic analysis demonstrated WHO Function Class(FC) Ⅲ/Ⅳ (OR=2.416,95%CI 1.016-5.743, P=0.046) and TBIL level (OR=6.874,95%CI 1.643-28.757, P=0.008) were the independent risk factors of perinatal complications. Conclusion: TBIL and WHO FC are independent risk factors of perinatal complications in pregnant women with pulmonary hypertension underwent cesarean section.

Impact of Spectators on a Two-Qubit Gate in a Tunable Coupling Superconducting Circuit.

Cross-resonance (CR) gates have emerged as a promising scheme for fault-tolerant quantum computation with fixed-frequency qubits. We experimentally implement an entangling CR gate by using a microwave-only control in a tunable coupling superconducting circuit, where the tunable coupler provides extra degrees of freedom to verify optimal conditions for constructing a CR gate. By developing a three-qubit Hamiltonian tomography protocol, we systematically investigate the dependency of gate fidelities on spurious qubit interactions and present the first experimental approach to the evaluation of the perturbation impact arising from spectator qubits. Our results reveal that the spectator qubits lead to reductions in CR gate fidelity dependent on ZZ interactions and particular frequency detunings between spectator and gate qubits. The target spectator demonstrates a more serious impact than the control spectator under a standard echo pulse scheme, whereas the degradation of gate fidelity is observed up to 22.5% as both the spectators are present with a modest ZZ coupling to the computational qubits. Our experiments uncover an optimal CR operation regime, and the method we develop here can readily be applied to improving other kinds of two-qubit gates in large-scale quantum circuits.

Inverse association between bone mineral density and fibrinogen in menopausal women.

OBJECTIVE: Inflammatory diseases are risk factors for osteoporosis. We aimed to explore whether fibrinogen, which is linked to chronic inflammation, is associated with bone mineral density (BMD) in menopausal women. METHODS: In this cross-sectional study, we analyzed 339 menopausal women from Zhejiang Province between January 2016 and October 2019. Linear regression analysis was performed to assess the relationship between fibrinogen and BMD. RESULTS: Significant inverse association was observed between the serum fibrinogen level and BMD in menopausal women. The mean BMD in each quartile of fibrinogen level was 0.901, 0.897, 0.892, and 0.855 g/cm2, respectively (p = 0.027). After adjusting for age, body mass index, metabolic profiles, blood inflammatory factors, and serum levels of estradiol, calcium, phosphorus, and alkaline phosphatase, fibrinogen levels remained significantly associated with BMD (regression coefficients for quartiles 1-3 vs. quartile 4 were 0.046, 0.027, and 0.036, respectively; p for trend <0.05). CONCLUSIONS: Higher fibrinogen levels were associated with lower BMD in menopausal women, which was independent of age, body mass index, estradiol, and other factors. Therefore, serum fibrinogen can be used as a new predictor of reduced BMD in menopausal women.

Inverse association between systemic immune-inflammation index and bone mineral density in postmenopausal women.

OBJECTIVE: The aim of the present study was to investigate whether systemic immune-inflammation index (SII) and neutrophil-to-platelet ratio (NLR) were associated with bone mineral density (BMD) in postmenopausal women. METHODS: In this cross-sectional study, we enrolled 413 postmenopausal women who never received menopause hormone therapy. The relationship between SII, NLR, and BMD was investigated by linear regression analysis. RESULTS: Significant inverse association was observed between SII and BMD in postmenopausal women. The mean BMD in each quartile of SII level were 0.923, 0.914, 0.900, and 0.876 g/cm2, respectively (p = .011). After adjusting for covariates, SII levels remained significantly associated with BMD (regression coefficients for quartiles 1-3 vs. quartile 4 were 0.035, 0.029, and 0.023, respectively; p for trend <.05). An inverse association was also found between NLR and BMD in postmenopausal women. However, there was no significant association between NLR and BMD after adjusting for covariates. CONCLUSION: The quartile of SII was negatively associated with the mean BMD in postmenopausal women, independent of age, body mass index, sex hormone levels, and other factors. Therefore, SII can be used as a new predictor of bone loss in postmenopausal women.

[Daratumumab for the treatment of primary systemic amyloidosis: a multicenter retrospective analysis].

Objective: To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis. Methods: Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed. Results: All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients. Conclusion: Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.