Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

Objective To explore the mechanism of Gandou Fumu Decoction(GDFMD)for improving Wilson's disease(WD)in tx-J mice.Methods With 6 syngeneic wild-type mice as the control group,30 tx-J mice were randomized into WD model group,low-,medium-and high-dose GDFMD treatment groups,and Fer-1 treatment group.Saline(in control and model groups)and GDFMD(3.48,6.96 or 13.92 g/kg)were administered by gavage,and Fer-1 was injected intraperitoneally once daily for 14 days.Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue;ALT,AST,albumin,AKP levels were determined to assess liver function of the mice.Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4,ACSL4,ALOX15,FTH1,FLT,TFR1,FAS,SCD1,and ACOX1,and Fe2+,MDA,ROS,SOD,GSH and 4-HNE levels were analyzed to assess oxidative stress.Results The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT,AST and AKP,decreased albumin level,increased Fe2+,MDA,ROS,4-HNE levels,decreased SOD and GSH levels(P<0.05),lowered protein expressions of ACOX1,GPX4,FTH1,FLT,FAS,and SCD1,and increased protein contents of TFR1,ACSL4 and ALOX15 in the liver.Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models,decreased the levels of Fe2+,MDA and ROS,increased SOD and GSH levels,and reversed the changes in hepatic protein expressions.Conclusion GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.

Objective To investigate the role and mechanism of RNA-Specific adenosine deaminase 3 (Adar3) in regulating macrophage polarization during Coxsackievirus B3(CVB3)-induced viral myocarditis (VM). Methods Bone marrow-derived macrophages (BMDM) from mice were cultured in vitro and induced into M1/M2 macrophages using interferon-gamma (IFN-γ)/lipopolysaccharide (LPS) or interleukin 4 (IL-4), respectively. The mRNA expression levels of Adar1, Adar2, and Adar3 in each group of cells were assessed by real-time quantitative PCR (qRT-PCR). Specific siRNAs targeting the Adar3 gene were designed, synthesized, and transiently transfected into M2 macrophages. The mRNA levels of M2 polarization-related marker genes-including arginase 1 (Arg1), chitinase 3-like molecule 3 (YM1/Chi3l3), and resistin-like molecule alpha (RELMα/FIZZ1)-were detected by qRT-PCR. RNA sequencing was performed to analyze the signaling pathways affected by Adar3. The expression levels of Wnt/β-catenin signaling pathway were further validated using qRT-PCR and Western blot. The adeno-associated virus overexpressing Adar3 was designed, synthesized, and injected into mice via tail vein. Three weeks later, a myocarditis mouse model was established. After an additional week, the phenotype and function of cardiac macrophages, as well as multiple indicators of VM (including echocardiography, body weight, histopathology and serology) were examined. Additionally, the protein levels of the Wnt/β-catenin signaling pathway were assessed. Results Compared to M0-type macrophages, the expression level of Adar3 was significantly increased in M2-type macrophages. After transfection of Adar3 siRNA, the mRNA levels of Arg1, YM1 and FIZZ1 in M2 macrophages were downregulated. RNA sequencing revealed 149 upregulated genes and 349 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and subsequent validation experiments indicated that Adar3 modulated the Wnt/β-catenin signaling pathway. In vivo experiments demonstrated that Adar3 overexpression alleviated the cardiac dysfunction of VM mice. The proportion of M1 macrophages in the heart decreased, while the proportion of M2 macrophages increased. At the same time, the Adar3 overexpression activated the Wnt/β-catenin signaling pathway. Conclusion Adar3 promotes macrophage polarization toward the M2 phenotype by activating the Wnt/β-catenin signaling pathway, thereby alleviating VM.
Animals ; Adenosine Deaminase/metabolism* ; Macrophages/immunology* ; Wnt Signaling Pathway/genetics* ; Myocarditis/immunology* ; Mice ; Coxsackievirus Infections/metabolism* ; Male ; Mice, Inbred BALB C ; Enterovirus B, Human/physiology* ; beta Catenin/genetics*

Objective:To evaluate the effect of sex factors on rewarming in patients with mild hypothermia undergoing lithotripsy for urolithiasis.Methods:In this prospective study, 100 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-60 yr, with a body mass index of 18-30 kg/m 2, scheduled for elective lithotripsy for urolithiasis, were divided into 2 groups ( n=50 each) based on sex: male group (group M) and female group (group F). The rewarming measures were as follows: the room was preheated, maintaining a constant temperature of 22-24 ℃, all the patients were covered with medical heating blanket under their bodies, and the inflatable heating apparatus was placed on the surface quilt, and the air supply was placed near the lower limbs of the patients. The parameters were set as follows: temperature 40 ℃, strong wind. If the patients complained of heat, the temperature parameter settings were changed, and the quilt was removed when necessary. If the patients complained of cold, blood transfusion and infusion heating instrument were added, medical heating blanket was turned on, or an anther quilt was used. Body temperature and the number of patients with successful rewarming were recorded on admission to post-anesthesia care unit (T 0) and at 10, 30, 45 and 60 min after rewarming (T 1-4), and at 1, 3 and 5 h after returning to the ward (T 5-7). The comfort scores were assessed while measuring body temperature at T 0 and T 4, and the occurrence of shivering, hypertension, hypotension and arrhythmias was observed. Results:Compared with group F, the body temperature was significantly increased at T 3 and T 4, the success rate of rewarming and incidence of shivering were increased at T 3 ( P<0.05), and no significant change was found in the incidence of hypertension, hypotension and arrhythmias in group M ( P<0.05). Conclusions:Sex factors affect rewarming outcomes in patients with mild hypothermia undergoing lithotripsy for urolithiasis. Females exhibit a slower rewarming rate and less shivering than males.

Objective:To explore the surgical efficacy of cervical cerclage with cervical length (CL) <10 mm and emergency cerclage.Methods:From January 2013 to June 2022, a total of 98 singleton pregnant women who underwent ultrasound-indicated cervical cerclage because of CL<10 mm in the second trimester and underwent emergency cervical cerclage because of cervical dilation found by physical examination in Peking University First Hospital were enrolled. The differences in clinical data between the <34 weeks delivery group (25 cases) and the ≥34 weeks delivery group (73 cases) were compared. Meanwhile, according to different cervical status, they were divided into CL<10 mm group (43 cases) and cervical dilatation group (55 cases), and the cervical dilatation group was further divided into cervical dilatation <4 cm group and cervical dilatation ≥4 cm group. The clinical data and pregnancy outcomes of pregnant women with different cervical status were compared.Results:(1) There were significant differences in the proportion of preoperative CL<10 mm and the degree of preoperative cervical dilation between the <34 weeks delivery group and the ≥34 weeks delivery group (all P<0.05). (2) After cervical cerclage, compared with women in the cervical dilatation group, the prolonged gestational age in the CL<10 mm group was longer [(10.5±4.6) vs (14.3±3.4) weeks], the gestational age at delivery was later (median: 35.7 vs 38.0 weeks), the preterm birth rates before 37 and 34 weeks were lower, the late abortion rate was lower [9% (5/55) vs 0 (0/43)], and the newborn birth weight was higher, the differences were statistically significant (all P<0.05). (3) Compared with the cervical dilation ≥4 cm group, the prolonged gestational age of the cervical dilatation <4 cm group was longer [(7.5±5.3) vs (11.1±4.2) weeks], the gestational age at delivery was later (median: 29.2 vs 36.0 weeks), and the birth weight of the newborn was higher (all P<0.05). The late abortion rate of cervical dilatation <4 cm group was lower than that of cervical dilatation ≥4 cm group [7% (3/45) vs 2/10; P=0.220]. Conclusions:Timely cervical cerclage in individuals with CL<10 mm could reduce preterm birth rate before 34 weeks gestation, and the pregnancy outcome is better than that of individuals with cervical dilation. Moreover, the pregnancy outcome of cervical cerclage in women with cervical dilation <4 cm is significantly better than that in women with cervical dilatation ≥4 cm.

Objective To analyze the endowment features of patients with primary angle-closure glaucoma(PACG)based on circuit-qi theory,thus to provide approaches for revealing the etiology,pathogenesis and prevalence of PACG.Methods From October 2023 to March 2024,a total of 204 patients with PACG admitted to the Eye Hospital,China Academy of Chinese Medical Sciences were enrolled into the analysis.The natal day of the patients was used for the calculation of conception day,and then the conception day was used for the analysis of the features of five circuits and six qi based on the stem-branch lunar year of conception day.A database of information of five circuits and six qi on conception day was constructed,and then the features of their endowments at conception were statistically analyzed.Results No statistically significant differences were shown in the distribution of the dominant qi,guest qi,sitian(celestial control)and zaiquan(terrestrial effect)at conception in PACG patients(P＞0.05),but there were statistically significant differences in the distribution of yearly circuit,comprehensive circuit-qi,and combined circuit-qi at conception in PACG patients(P＜0.05).Most of PACG patients had the circuit-qi features of shaomu(deficiency of wood)-yangming dryness gold-shaoyin monarch fire,and taitu(excess of earth)-shaoyin monarch fire-yangming dryness gold at conception.Conclusion Those who are conceived at the date with circuit-qi features of shaomu and taitu,comprehensive circuit-qi features of shaomu-yangming dryness gold-shaoyin monarch fire and taitu-shaoyin monarch fire-yangming dryness gold,and combined circuit-qi features of shunhua(qi generating circuit)and celestial restriction(qi restricting circuit)are vulnerability to PACG.The development of the constitution of PACG patients may be related to the congenital circuit-qi features of pathogenic dryness attacking the lung,and metal exuberance restricting wood.

Objective To evaluate the clinical value of portable ultrasound in the management of traumatic shock patients.Methods From September 2020 to October 2021,52 patients with traumatic shock were admitted to Department of Emergency of The First Affiliated Hospital of Naval Medical University and underwent abdominal ultrasound and CT plain scan.The accuracy of ultrasound was compared with surgical or CT results which were taken as the gold standard.The time taken before,during,and after ultrasound and CT examinations were recorded.Working years of the sonographers were also recorded.Results In traumatic shock patients,the coincidence rates of ultrasound diagnosis of effusion and abdominal organ injuries were 85%and 82%,respectively.Ultrasound had shorter time interval from admission to first examination,shorter time to obtain test results,shorter total time,and longer testing time than CT(P<0.05).The average time of examination by sonographers with 3 and more working years was significantly shorter than that by sonographers with less than 3 working years([5.06±1.20]min vs.[6.14±1.29]min,P<0.05).Conclusion Portable ultrasound can provide rapid and accurate diagnosis of abdominal organ injuries and thoracic/abdominal effusions in traumatic shock patients,with significantly shorter total evaluation time compared with CT.Proficiency-gained sonographers can further optimize examination efficiency,proving particularly valuable for time-critical resuscitation.

OBJECTIVES: To explore the mechanism of Gandou Fumu Decoction (GDFMD) for improving Wilson's disease (WD) in tx-J mice. METHODS: With 6 syngeneic wild-type mice as the control group, 30 tx-J mice were randomized into WD model group, low-, medium- and high-dose GDFMD treatment groups, and Fer-1 treatment group. Saline (in control and model groups) and GDFMD (3.48, 6.96 or 13.92 g/kg) were administered by gavage, and Fer-1 was injected intraperitoneally once daily for 14 days. Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue; ALT, AST, albumin, AKP levels were determined to assess liver function of the mice. Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4, ACSL4, ALOX15, FTH1, FLT, TFR1, FAS, SCD1, and ACOX1, and Fe²⁺, MDA, ROS, SOD, GSH and 4-HNE levels were analyzed to assess oxidative stress. RESULTS: The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT, AST and AKP, decreased albumin level, increased Fe²⁺, MDA, ROS, 4-HNE levels, decreased SOD and GSH levels (P<0.05), lowered protein expressions of ACOX1, GPX4, FTH1, FLT, FAS, and SCD1, and increased protein contents of TFR1, ACSL4 and ALOX15 in the liver. Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models, decreased the levels of Fe²⁺, MDA and ROS, increased SOD and GSH levels, and reversed the changes in hepatic protein expressions. CONCLUSIONS GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Mice ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Hepatolenticular Degeneration/drug therapy* ; Hepatocytes/metabolism* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Fatty Liver/metabolism* ; Arachidonate 15-Lipoxygenase/metabolism* ; Coenzyme A Ligases/metabolism* ; Liver/metabolism* ; Male

AIM:To evaluate the characteristics of ocular biometric parameters and the distribution of corneal astigmatism(CA)in patients with high myopia before cataract surgery.METHODS:A prospective cross-sectional study was conducted, and 695 cataract patients(695 eyes)with high myopia [defined as an axial length(AL)≥26.00 mm] scheduled to undergo cataract surgery at our hospital from January 2022 to December 2024 were consecutively enrolled, another 695 cataract patients(695 eyes)with normal ALs(22.00 mm ≤AL≤25.00 mm)who underwent cataract surgery at our hospital during the same period were included in the control group. For patients with both eyes eligible, the right eye was used for analysis. Before cataract surgery, IOL Master 700 was used to measure the ocular biometric parameters of both eyes for each patient in the two groups. The medical records and ocular biometric data in the two groups were recorded and collected.RESULTS:There were no statistically significant differences between the two groups in genger, age, corneal diameter, and central corneal thickness(all P>0.05). In the high myopia group, the mean AL was 29.20±2.61 mm, and 252 eyes(34.1%)had AL ≥30.00 mm(extremely high myopia). The mean anterior chamber depth(ACD), lens thickness, vitreous chamber depth(VCD), CA, AL/corneal radius of curvature and VCD/AL in the high myopia group were 3.45±0.40, 4.41±0.47, 21.34±2.60 mm, 1.18±0.78 D, 3.79±0.38, and 0.73±0.03, respectively, which were all greater than those in the control group(all P<0.01). In the high myopia group, 350 eyes(50.4%)had CA ≥1.00 D, 192 eyes(27.6%)had CA ≥1.50 D, and 94 eyes(13.5%)had CA ≥2.00 D, which were all higher than those in the control group(32.8%, 15.1%, and 6.6%, respectively; all P<0.001). In the high myopia group, 87 eyes(12.5%)had flat corneas, 424 eyes(61.0%)had moderate CA, and 40 eyes(5.8%)had high CA. These proportions were all higher than those in the control group(6.0%, 46.9%, and 2.9%, respectively; all P<0.001). In the high myopia group, ACD and ACD/AL were negatively correlated with AL(r=-0.162 and -0.661, respectively; all P<0.001), while both ACD and ACD/AL in the control group were positively correlated with AL(r=0.338 and 0.105, respectively; both P<0.01). In the high myopia group, CA increased with age when the patient's age was ≥50 years(r=0.197, P<0.001), which was consistent with the control group.CONCLUSION: The standardized ocular biometric data of cataract patients with high myopia before cataract surgery are helpful for ophthalmologists to accurately calculate the intraocular lens(IOLs)power and select the appropriate IOL type. The majority of high myopia patients need simultaneous correction of CA during cataract surgery.

BACKGROUND:Successful uterine spiral artery remodeling is necessary for normal pregnancy,in which vascular smooth muscle cells are important cells.Interferon-γ is associated with the loss of vascular smooth muscle cells during early pregnancy.However,the specific mechanism is not fully understood. OBJECTIVE:To investigate the effects of interferon-γ on migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway. METHODS:Human vascular smooth muscle cells were divided into control group and interferon-γ group.The control group was cultured normally,and the interferon-γ group was treated with 10 ng/mL interferon-γ for 24 hours.The migration ability of vascular smooth muscle cells was detected by Transwell assay.The apoptosis of vascular smooth muscle cells was detected by TUNEL assay and flow cytometry.The mRNA expression levels of NLRP3 and caspase-1 were detected by qPCR.Western blot assay was utilized to detect NLRP3,caspase-1,and cleaved N-terminal GSDMD protein expression levels. RESULTS AND CONCLUSION:Compared with the control group,the migration ability and apoptosis rate of vascular smooth muscle cells in interferon-γ group were significantly increased(P<0.05).Compared with the control group,the mRNA expression levels of NLRP3 and caspase-1 in vascular smooth muscle cells of interferon-γ group were significantly increased(P<0.05).Compared with control group,the expression levels of NLRP3,caspase-1,and cleaved N-terminal GSDMD protein in vascular smooth muscle cells in the interferon-γ group were significantly increased(P<0.05).The results suggest that interferon-γ may regulate the migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway.