Autoimmune hepatitis （AIH） is an autoimmune disease characterized by liver parenchymal destruction and chronic fibrosis， and it is often mediated by T cells. The pathogenesis of AIH involves multiple factors， including sex， region， environmental factors， and genetic susceptibility. A notable predisposition is observed in female individuals， and the incidence rate of AIH in female individuals is significantly higher than that in male individuals. This sex difference is associated with various factors， and sex hormones may be an important cause of the female predominance of AIH， although the specific mechanisms remain unclear. An in-depth understanding of the mechanism of action of sex hormones in the pathogenesis of AIH will help to better understand the pathogenesis of the disease and may provide important clues for developing future treatment methods and prevention strategies. This article reviews the mechanism of action of estrogen and androgen in regulating the pathogenesis of AIH by regulating T cells， in order to provide new ideas and directions for further exploring the potential role of sex hormones in the etiology of autoimmune diseases.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

Objective Compared with endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA),this study aims to explore the diagnostic advantages of endobronchial ultrasound-guided transbronchial node biopsy(EBUS-TBNB)in the diagnosis of mediastinal lymph node metastasis,lymphadenitis,sarcoidosis and other mediastinal lymph node diseases associated with mediastinal enlargement in lung cancer and extra-pulmonary tumors.Methods The detection rate of malignant tumor was(14/35,40％)by EBUS-TBNA and average amount of bleeding during each operation was 1-2 mL;Compared with EBUS-TBNA,the detection rate of malignant tumors by EBUS-TBNB was(23/35,66％)(P＜0.01),and 4 cases of granulomas were diagnosed,and the average amount of bleeding during each operation was 3-4 mL.Conclusions Compared with EBUS-TBNA,EBUS-TBNB has a higher detection rate for malignant tumors and has more advantages in the diagnosis of benign proliferative dis-eases.It can further improve the accuracy and sensitivity of diagnosing mediastinal enlarged lymph nodes so is wor-thy of clinical promotion and application.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

Feature extraction methods and classifier selection are two critical steps in heart sound classification. To capture the pathological features of heart sound signals, this paper introduces a feature extraction method that combines mel-frequency cepstral coefficients (MFCC) and power spectral density (PSD). Unlike conventional classifiers, the adaptive neuro-fuzzy inference system (ANFIS) was chosen as the classifier for this study. In terms of experimental design, we compared different PSDs across various time intervals and frequency ranges, selecting the characteristics with the most effective classification outcomes. We compared four statistical properties, including mean PSD, standard deviation PSD, variance PSD, and median PSD. Through experimental comparisons, we found that combining the features of median PSD and MFCC with heart sound systolic period of 100-300 Hz yielded the best results. The accuracy, precision, sensitivity, specificity, and F1 score were determined to be 96.50%, 99.27%, 93.35%, 99.60%, and 96.35%, respectively. These results demonstrate the algorithm's significant potential for aiding in the diagnosis of congenital heart disease.
Humans ; Heart Sounds ; Neural Networks, Computer ; Algorithms ; Heart Defects, Congenital

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl₄, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl₄-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl₄-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

Objective:To develop a model of stellate ganglion block (SGB) in mice and investigate the effect of SGB on cerebral cortical blood flow.Methods:Thirty clean-grade healthy male C57BL/6 mice, aged 8-9 weeks, weighing 23-27 g, were divided into 5 groups ( n=6 each) using a random number table method: control group (group C), left SGB group (group L), left normal saline group (group SL), right SGB group (group R) and right normal saline group (group SR). Group C received no intervention.SGB was performed with 0.25% ropivacaine 0.08 ml via percutaneous posterior approach in L and R groups, while the equal volume of normal saline 0.08 ml was given instead at the location of left and right stellate ganglion in SL and SR groups, respectively.The cerebral cortical blood flow was determined using laser speckle contrast imaging system before SGB (T 0) and at 10, 30, 60, 90 and 120 min after SGB (T 1-5). Results:Mice developed ptosis on the block side, indicating that the model of SGB was successfully developed in L and R groups.There was no significant difference in cerebral cortical blood flow at each time point among C, SL and SR groups ( P>0.05), and cerebral cortical blood flow on the block side decreased at T 1, began to increase at T 2, peaked at T 3, and decreased at T 5 which was still higher than that at T 0 in group L and group R ( P<0.01). Compared with C and SL groups, the left cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group L ( P<0.01). Compared with C and SR groups, the right cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group R ( P<0.01). There were no significant differences in cerebral cortical blood flow at each time point between group C and group SL and between group C and group RL ( P>0.05). Conclusions:The mouse model of SGB via percutaneous posterior approach is successfully developed.Unilateral SGB can affect cerebral cortical blood flow on the block side, which shows a transitory decrease followed by a sustained significant increase.

With the economic development and medical progress in China, the incidence of prostate cancer is increasing, and most patients have already developed advanced tumors with poor prognosis when diagnosed. The main cornerstone of treatment for metastatic hormone-sensitive prostate cancer (mHSPC) has always been androgen deprivation therapy (ADT), but most mHSPC will transform into metastatic castration-resistant prostate cancer (mCRPC), how to prolong the time from mHSPC to mCRPC has become a current research hotspot, and several landmark phase 3 clinical trials in recent years have led to rapid changes in patient treatment options, including a variety of drugs with different mechanisms of action (e.g., endocrine therapy, chemotherapy, radiotherapy, immunotherapy, and targeted therapy). This article will focus on the current status and progress of novel endocrine agents in metastatic prostate cancer for clinical use.

Objective:To evaluate the effect of age on mood of patients during induction of general anesthesia with remimazolam.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱpatients of both sexes, undergoing elective surgery with general anesthesia requiring tracheal intubation, aged 5-80 yr, with body mass index 18-30 kg/m 2, were divided into 4 groups ( n=20 each) according to different ages: juvenile group (R 1 group, 5-17 yr), youth group (R 2 group, 18-44 yr), middle-aged group (R 3 group, 45-59 yr) and elderly group (R 4 group, 60-80 yr). Remimazolam was intravenously injected in a loading dose of 0.1 mg/kg for induction of general anesthesia, followed by an infusion of 0.1 mg·kg -1·h -1 for maintenance of general anesthesia, and the other anesthetics for induction and maintenance of anesthesia were all the same in each group.The changes in emotion and brain wave within 3 min after remimazolam injection were recorded.The brain waves and Modified Observer′s Assessment of Alertness and Sedation (MOAA/S) scale score were recorded at 1, 2 and 3 min after administration.Adverse effects during anesthesia induction were also recorded. Results:Compared with group R 1, the incidence of happy mood was significantly decreased, the grade of mood was decreased, and the dream Likert score and MOAA/S score were decreased in R 3 and R 4 groups, and the dream Likert score and MOAA/S score were decreased in group R 2, and the incidence of hypoxemia during induction of general anesthesia was increased in group R 4( P<0.01). Compared with group R 2, the incidence of happy mood was significantly decreased in R 3 and R 4 groups, and MOAA/S score was significantly decreased in group R 4 ( P<0.05). Compared with R 1 and R 2 groups, the proportion of beta bands was significantly decreased, and the proportion of theta and delta bands was increased in R 3 and R 4 groups ( P<0.01). Compared with group R 3, the proportion of beta band was significantly decreased, and the proportion of delta band was increased in group R 4 ( P<0.01). Conclusion:Remimazolam 0.1 mg/kg used for induction of general anesthesia can cause happy mood, accompanied by enhanced brain electrical signal activity of beta band, especially in the patients under 45 yr of age.

Objective This study was conducted to evaluate treatment-related toxicities,the patterns of failure,overall survival(OS)and progression-free survival(PFS)by comparing IFI with ENI in combination with chemotherapy. Methods Eligible patients were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. The primary end points wereacute treatment-related toxicities. The secondary end points were patterns of failure,OS and PFS. Kaplan?Meier survival rate of the method for calculating the Logrank test difference method. Results Between April 2012 and October 2016,a total of 228 patients were enrolled from nine centers in china. Grade≥3,Grade≥2 radiation esophagitis and pneumonitis in the IFI arm were significantly lower than that of the ENI arm(P=0.018,0.027).No significant differences were observed in overall failure rates,loco-regional failure,distant failure rates,in-field and out-field lymph node failure between the two arms(P=0.401,0.561,0.510,0.561,0.681).The 1-,2-, 3-,4-yearand median OS in the ENI arm and IFI arm were 84.1%,57.3%,39.4%,31.6%,28 months and 83.6%,62.1%,44.5%,31.5%,32 months(P=0.654),respectively. The 1-,2-,3-yearand median PFS in the ENI arm and IFI arm were 71.9%,42.3%,32.7%,20 months and 70.1%,45.0%,35.9%,22 months (P=0.885),respectively. Conclusions Compared to ENI,IFI resulted in decreased radiation pneumonitis and esophagitis without sacrificing loco-regional lymph nodal control,PFS and OS in thoracic ESCC. Clinical Trial Registry Chinese Clinical trail registry,registration number:NCT01551589.