Objective:To investigate the impact of the interval period between biopsy and MR examination on tumor detection and extraprostatic extension (EPE) assessment for prostate cancer (PCa) using multi-parametric MRI (mpMRI).Methods:The study was cross-sectional and retrospectively included 130 patients with PCa who underwent RP and preoperative systematic biopsies followed by mpMRI between January 2021 and December 2022 in the First Medical Center of Chinese PLA General Hospital. Patients were divided into 3 groups according to interval following biopsy (group A,<3 weeks, 31 cases; group B, 3-6 weeks, 67 cases; group C,>6 weeks, 32 cases). The percentages of hemorrhage volume in the total prostate were drawn on T 1WI and calculated. The junior, senior and expert radiologists independently localized the index lesions and calculated the accuracy for tumor detection, in addition to assessing the probabilities of EPE according to EPE grade. The correlation between the hemorrhage extent and interval was analyzed using the Spearman correlation coefficient. The accuracy for tumor detection was compared using χ2 test among groups. The diagnostic performance of the radiologists for EPE prediction was assessed using the receiver operating characteristic curve, and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. Results:The percentage of hemorrhage was correlated with the interval between biopsy and MR examination ( r=-0.325, P<0.001). The detection accuracy of junior radiologist was 83.9% (26/31), 76.1% (51/67), and 78.1% (25/32) in group A, B and C, respectively; no differences were observed in the detection accuracy among three groups ( χ2=0.76, P=0.685). The detection accuracy of senior radiologist was 83.9% (26/31), 80.6% (54/67), and 71.9% (23/32) in 3 groups with no differences ( χ2=1.53, P=0.464). The detection accuracy of expert radiologist was 80.6% (25/31), 77.6% (52/67), and 93.8% (30/32) with no differences ( χ2=3.95, P=0.139). The AUC (95% CI) for predicting EPE were 0.830 (0.652-0.940), 0.704 (0.580-0.809), 0.800 (0.621-0.920) in the group A, B and C for junior radiologist; 0.876 (0.708-0.966), 0.768 (0.659-0.863), 0.896 (0.736-0.975) for senior radiologist; and 0.866 (0.695-0.961), 0.813 (0.699-0.895), 0.852 (0.682-0.952) for expert radiologist, respectively. No differences were observed among the subgroups in each radiologist ( P>0.05). Conclusion:The interval period does not significantly affect the detection accuracy and EPE assessment of PCa using mpMRI. There is probably no necessity for prolonged intervals following systematic biopsy to preserve the clarity of MRI interpretation for PCa.

OBJECTIVE To evaluate the ameliorative effect of Juanbi Tongluo Oral Liquid on sciatic neuronal apoptosis in Type 2 diabetic model mice.METHODS The Type 2 diabetes mouse model was established by feeding with high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin(STZ).The mice were treated with metformin(200 mg·kg-1·d-1),low dose(3.9 g·kg-1·d-1)and high dose(7.8 g·kg-1·d-1)Juanbi Tongluo Oral Liquid for 35 days.The latency of response to thermal stimu-lation was detected by hot plate,and the values of blood glucose insulin and glycosylated hemoglobin were determined.Biochemical kits were used to detect the expression of serum total cholesterol(T-CHO),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and oxidation product malondialdehyde(MDA).The expression of tumor cytokine α(TNF-α),interleukin(IL)-1β,IL-6 and IL-10 in serum of mice were detected by ELISA method;the injury of sciatic nerve of model mice was detected by HE staining;the apoptosis of sciatic nerve was detected by TUNEL method;and the expression of neurofilament protein NF-L,apoptosis(cleaved Caspase-3,Caspase-3)and oxidative stress(Nrf2,HO-1)signal pathway proteins in sciatic nerve of model mice were detected by Western blot method.RESULTS High-dose Juanbi Tongluo Oral Liquid shortened the latent period of heat pain response in model mice(P<0.01);downregulated fasting blood glucose and glycated hemoglobin(P<0.01),and upregulated fasting plasma insulin in model mice(P<0.01);downregulated serum T-CHO,TG,and LDL-C levels(P<0.01),upregulated HDL-C levels(P<0.01);downregulated serum pro-inflammatory factors TNF-α,IL-1β and IL-6 levels(P<0.05),upregulated the anti-inflammatory cyto-kine IL-10 level(P<0.01);inhibited sciatic nerve structural damage and apoptosis(P<0.05);downregulated the ratio of cleaved Caspase-3 to Caspase-3 in the apoptosis pathway(P<0.01);upregulated the expression of neurofilament proteins NF-L and NF-H in sciatic nerve tissue(P<0.05,P<0.01);and upregulated the expression of antioxidant stress proteins Nrf2 and HO-1(P<0.01).CONCLUSION Juanbi Tongluo Oral Liquid can improve sciatic neuronal apoptosis of Type 2 diabetic mice,which may be related to its effect on improving oxidative stress and inflammatory stress.

Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients. Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM. Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups. Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

Objective:To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency.Methods:This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively.Results:The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders.Conclusions:Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Objective:To analyze the efficacy of laparoscopic radical surgery, compared to open surgery, for incidental gallbladder cancer following cholecystectomy.Methods:Clinical data of 106 patients with incidental gallbladder cancer treated at the Second Affiliated Hospital Zhejiang University School of Medicine from April 2010 to February 2018 were retrospectively analyzed, including 66 males and 40 females, aged (64.7±7.9) years old. According to surgical approach, patients were divided into the laparoscopic group ( n=45) and open group ( n=61). Perioperative data, including intraoperative blood loss, postoperative hospital stay, and postoperative complications, were compared between the groups. Follow-ups were conducted via outpatient visits or telephone reviews. Survival analysis was performed using the Kaplan-Meier method, and the survival rates were compared using the log-rank test. Results:All 45 patients in the laparoscopic group successfully underwent the surgery without conversion to open surgery. Compared to the open group, the laparoscopic group had a reduced intraoperative blood loss [(100±25) ml vs. (200±46) ml] and a shortened postoperative hospital stay [3(2, 5) d vs. 5(4, 7) d] (both P<0.05). The postoperative complication rates were 6.7% (3/45) in the laparoscopic group and 13.1% (8/61) in the open group ( χ2=4.16, P=0.041). The cumulative survival rate after radical surgery for incidental gallbladder cancer was better in the laparoscopic group ( χ2=4.58, P=0.032). Conclusion:Compared to open surgery, laparoscopic radical surgery for incidental gallbladder cancer showed benefits in intraoperative blood loss, postoperative hospital stay, complication rates, and cumulative survival.

BACKGROUND: Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients. METHODS: Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes. RESULTS: Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality. CONCLUSION: Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients. CLINICAL TRIAL REGISTRATION Chinese Clinical Trail Registry, No. ChiCTR2100044625.
Humans ; Blood Pressure ; Pulmonary Disease, Chronic Obstructive/therapy* ; Cohort Studies ; Respiration, Artificial ; Inpatients ; Hospital Mortality

Objectives:To investigate the effect of fat suppression (FS) T 2WI on the interobserver agreement and diagnostic performance of clear cell likelihood score version 2.0 (ccLS v2.0) for clear cell renal cell carcinoma (ccRCC). Methods:In this retrospective study, the MR images of 111 patients with pathologically confirmed small renal masses (SRM) from January to December 2021 were analyzed in the First Medical Centre, Chinese PLA General Hospital. Of the 111 SRM, 82 cases were ccRCC and 29 cases were non-ccRCC. Two radiologists independently assessed ccLS scores based on T 2WI signal intensity (hypointense, isointense, hyperintense) and other MRI features (ccLS-T 2WI). After a one-month interval, the ccLS scores were independently evaluated utilizing the frequency-selective saturation FS-T 2WI and other MRI features (ccLS-FS-T 2WI). Fisher′s exact test was used to compare the difference in SRM signal intensity on T 2WI and FS-T 2WI. The weighted Kappa test was performed to assess the interobserver agreement of the two radiologists, and differences in the weighted Kappa coefficients were compared using the Gwet consistency coefficient. Receiver operating characteristic curves were drawn to evaluate the diagnostic performance of ccLS-T 2WI and ccLS-FS-T 2WI in diagnosing ccRCC, and the area under the curve (AUC) was compared utilizing the DeLong test. Results:The signal intensity of 111 SRM on T 2WI and FS-T 2WI had statistically significant difference (χ 2=126.33, P<0.001), consistent in 88 cases (79.3%) and varied in 23 cases (20.7%). The weighted Kappa coefficient of ccLS-T 2WI was 0.57 (95%CI 0.45-0.69) between the two radiologists, and the weighted Kappa coefficient of ccLS-FS-T 2WI was 0.55 (95%CI 0.42-0.67), and the difference was not statistically significant ( t=-0.65, P=0.520). The AUC of ccLS-T 2WI for ccRCC diagnosis was 0.92 (95%CI 0.86-0.97), while the AUC of ccLS-FS-T 2WI for ccRCC diagnosis was 0.91 (95%CI 0.85-0.96), and the difference was not statistically significant ( Z=1.50, P=0.133). Conclusions:The interobserver agreement and diagnostic performance of ccLS v2.0 based on T 2WI and FS-T 2WI sequences for ccRCC are comparable, and FS-T 2WI is applicable for the clinical application of ccLS v2.0.

Objective: To explore the value of T2WI and enhanced T1WI magnetic resonance imaging models in differentiating inverted papilloma and polyp of nasal cavity and paranasal sinus． Methods: 54 cases of inverted papilloma (NIP) and 51 cases of polyp ( NP) with complete T2WI and enhanced T1WI images confirmed by pathology were collected．ITK snap was used to outline all levels of the lesion．Pyromics was used to extract image omics features．Firstly，the mRMR) was used for feature extraction，and then rfe-SVM was used to remove the feature of minimum score and establish a prediction model．The sensitivity and specificity of ROC curve were used to evaluate the performance of the model，and were verified in the validation set. Results: A total of 1 133 image omics features were extracted，and 30 features were retained after mrmr dimensionality reduction for the establishment of prediction models．The AUC value of T1WI enhanced prediction model was : training set 0. 98，validation set 0. 95，the sensitivity and specificity of training set were 89. 7% and 100% respectively，and the sensitivity and specificity of validation set were 93. 8% and 93. 3% respectively．The AUC value of T2WI prediction model was : training set 0. 95，validation set 0. 91，the sensitivity and specificity of training set were 82. 1% and 95. 6% respectively，and the sensitivity and specificity of validation set were 93. 8% and 84. 2% respectively． Conclusion MRI based on T1WI enhancement prediction model and T2WI prediction model have certain value in differentiating inverted papilloma and polyp of nasal cavity and paranasal sinus.

As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence.

Bivalves are species-rich mollusks with prominent protective roles in coastal ecosystems.Across these ancient lineages,colony-founding larvae anchor themselves either by byssus produc-tion or by cemented attachment.The latter mode of sessile life is strongly molded by left-right shell asymmetry during larval development of Ostreoida oysters such as Crassostrea hongkongensis.Here,we sequenced the genome of C.hongkongensis in high resolution and compared it to reference bivalve genomes to unveil genomic determinants driving cemented attachment and shell asymmetry.Importantly,loss of the homeobox gene Antennapedia(Antp)and broad expansion of lineage-specific extracellular gene families are implicated in a shift from byssal to cemented attachment in bivalves.Comparative transcriptomic analysis shows a conspicuous divergence between left-right asymmetrical C.hongkongensis and symmetrical Pinctada fucata in their expression profiles.Especially,a couple of orthologous transcription factor genes and lineage-specific shell-related gene families including that encoding tyrosinases are elevated,and may cooperatively govern asymmet-rical shell formation in Ostreoida oysters.