Discovery of potential inhibitors targeting SARS-CoV-2 Mpro.

OBJECTIVE: The coronavirus disease (COVID-19) pandemic, resulting from human-to-human transmission of a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has caused a global health emergency. The lack of a specific drug or treatment strategy against this disease makes it devastating. Given that the main protease (Mpro) of SARS-CoV-2 plays an indispensable role in viral polyprotein processing, its successful inhibition prevents viral replication and constrains virus spread. Therefore, developing an effective SARS-CoV-2 Mpro inhibitor to treat COVID-19 is imperative. MATERIALS AND METHODS: We employed a high-throughput screening (HTS) method based on fluorescence polarization (FP) assay and further confirmed by the fluorescence resonance energy transfer (FRET) method for the discovery of Mpro inhibitors. Then multiple approaches were taken to investigate the inhibition profiles of the hit compounds against Mpro, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assay, surface plasmon resonance analysis (SPR), high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (HPLC-Q-TOF-MS), cytopathic effect (CPE) assay, molecule docking, and the drug-likeness analysis. RESULTS: In this study, four Mpro inhibitors with low toxicity were selected from HTS. According to SPR, all the hit compounds had medium binding affinities toward SARS-CoV-2 Mpro. HPLC-Q-TOF-MS results revealed the non-covalent linkage of each compound with SARS-CoV-2 Mpro. Molecule docking simulated the molecule interactions between each compound and the substrate binding pocket of SARS-CoV-2 Mpro. CPE assay was used to detect their inhibitory activities against coronaviruses HCoV-OC43 and HCoV-229E. In particular, the IMB63-8G compound demonstrated the highest antiviral potency [50% effective concentration (IC50) value of 1.71 µg/mL] and selectivity against HCoV-OC43 (SI = 39), which was more than 4-fold higher than that of ribavirin (RBV). Besides, the IMB63-8G compound possessed favorable drug-likeness characteristics. CONCLUSIONS: Our results will highlight the therapeutic potential of these compounds for the treatment of SARS-CoV-2 infection.

Effect of moderate-intensity aquatic treadmill exercise on cognitive function and cerebral blood flow for healthy older adults.

To compare the effect of moderate-intensity aquatic treadmill exercise (ATM) on cerebral blood flow (CBF) and cognitive function in healthy older adults to that of moderate-intensity land-based treadmill exercise (LTM). This randomized controlled trial study was conducted between May 2023 and Oct 2023. Twenty-eight participants aged 60-80 were randomly assigned to either ATM group (N = 14) or LTM group (N = 14). Cognitive function and cerebral blood flow were assessed before and after the exercise. The outcome measures used in this study were the Digit Symbol Substitution Test (DSST) and the Digit Span Test (DST) to assess cognitive performance, and the mean middle cerebral artery blood velocity (MCAvmean) to evaluate CBF. A mixed effects model was used to analyze the within-group and between-group differences in cognitive function and CBF outcomes pre-to-post treadmill by SPSS. The DSST demonstrated a statistically significant improvement within both the ATM [ß ±â€¯SE: -13.643 ±â€¯2.407, 95 % CI: -18.749, -8.537] and LTM [ß ±â€¯SE: -19.25 ±â€¯3.66, 95 % CI: -26.424, -12.076] groups, indicating clinical significance in both groups. Both ATM and LTM groups exhibited post-exercise improvements within their respective groups for forward Digit Span Test (FDST) [ATM ß ±â€¯SE: -0.143 ±â€¯0.362, 95 % CI: -0.92, 0.634; LTM ß ±â€¯SE: -0.286 ±â€¯0.37, 95 % CI: -1.078, 0.506] and backward Digit Span Test (BDST) (ATM ß ±â€¯SE: -1.741 ±â€¯5.377, 95 % CI: -13.27, 9.792; LTM ß ±â€¯SE: -6.729 ±â€¯5.370, 95 % CI: -4.788, 18.24). In terms of MCAvmean, there is a higher improvement of CBF in ATM group [ß ±â€¯SE: -138.669 ±â€¯67.9217, 95 % CI: -288.164, 10.826] than LTM group [ß ±â€¯SE: -9.305 ±â€¯70.076, 95 % CI: -153.617, 135.007]. Hence, a single bout of moderate-intensity ATM and LTM can enhance cognitive function and CBF in healthy older adults, suggesting their potential as preventive strategies against age-related declines.

[Isolated rectal tuberculoma diagnosed after endoscopic surgery: a case report].

Intestinal tuberculosis commonly affects the ileocecal area and the terminal ileum, and is extremely rare in the rectum, with isolated rectal involvement being even rarer. This paper described a case of an isolated rectal tuberculoma in a female patient of 44 years old, Yi ethnicity, who was admitted to the hospital with abdominal distension and constipation. She had a history of hepatitis B virus infection. A colonoscopy revealed a rectal mass, and an endoscopic resection was performed. Post-operative pathological examination confirmed rectal tuberculosis, with no evidence of extra-rectal tuberculosis infection found. The final diagnosis was an isolated rectal tuberculoma. In cases where endoscopic examination suggests a rectal tumor, especially in patients with immunosuppressive conditions such as HIV or diabetes, the possibility of tuberculoma should be considered.

Effect of goose-derived adiponectin peptide gADP3 on LPS-induced inflammatory injury in goose liver.

1. This study evaluated the effects and mechanisms of action of the peptide gADP3 on hepatic inflammatory injury induced by lipopolysaccharide (LPS).2. Hepatic inflammatory injury was induced in geese by intraperitoneal injection of LPS and gADP3, and the adiponectin receptor agonist AdipoRon (positive control) was used for potential amelioration. Serum inflammatory factor levels, liver function-related biochemical indicators and oxidative stress-related biochemical parameters in the liver tissues were determined. The expression levels of adiponectin and its receptors, inflammation and oxidative stress-related genes and key signalling molecules involved in adiponectin, inflammation and oxidative stress signalling pathways in liver tissues were detected.3. The peptide gADP3 alleviated inflammatory cell infiltration and hepatic inflammatory changes, reversed the decrease in serum albumin (ALB), total protein (TP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) content or activity induced by LPS and increased the activity of the antioxidant enzymes CAT (catalase), SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase).4. The peptide gADP3 upregulated the expression of antioxidant enzyme-related genes GCLC, HO-1 and NQO1 in liver tissues, decreased the levels of inflammatory factors like TNF-α, IL-1ß, IL-6, IFN-γ and TGF-ß and reduced mRNA expression levels of inflammatory-related genes TNF-α, IL-1ß, iNOS and TGF-ß. Additionally, it increased the mRNA and protein expression levels of adiponectin and its receptors, as well as key molecules in the adiponectin signalling pathway like AMPK and PPARα. In addition, gADP3 reversed the changes in mRNA or protein expression of inflammatory and oxidative stress signalling pathway-related genes P38MAPK, NF-κBP65, TLR4 and Nrf2 in liver tissues caused by LPS treatment.5. In conclusion, goose-derived adiponectin peptide gADP3, similar to the adiponectin receptor agonist AdipoRon, attenuated LPS-induced hepatic inflammatory injury in geese.

Hetero-oligomeric interaction as a new regulatory mechanism for protein arginine methyltransferases.

Protein arginine methylation is a versatile post-translational protein modification that has notable cellular roles such as transcriptional activation or repression, cell signaling, cell cycle regulation, and DNA damage response. However, in spite of their extensive significance in the biological system, there is still a significant gap in understanding of the entire function of the protein arginine methyltransferases (PRMTs). It has been well-established that PRMTs form homo-oligomeric complexes to be catalytically active, but in recent years, several studies have showcased evidence that different members of PRMTs can have cross-talk with one another to form hetero-oligomeric complexes. Additionally, these heteromeric complexes have distinct roles separate from their homomeric counterparts. Here, we review and highlight the discovery of the heterodimerization of PRMTs and discuss the biological implications of these hetero-oligomeric interactions.

[Analysis of factors for anxiety and anxiety tendency in tinnitus patients].

Objective: To explore the related factors of anxiety and anxiety tendency in patients with tinnitus. Methods: A cross-sectional study was carried out. Basic information, tinnitus characteristics, and psychological status of patients who complained of tinnitus in the Outpatient Department of Eye & ENT Hospital, Fudan University between January 2020 and December 2023 were collected. All patients filled out the self-rating anxiety scale (SAS) and underwent pure tone audiometry testing. According to the SAS scores, patients were divided into three groups: non-anxiety group (SAS<40), anxiety tendency group (40≤SAS<50), and anxiety group (SAS≥50). The related factors of anxiety and anxiety tendency were analyzed using multivariate ordered logistic regression analysis. Results: A total of 176 patients (57 males and 119 females) aged (49.4±10.7) years (range: 13-76 years)were included, with the onset time of 3 days-37 years. There were 78 cases (44.3%), 65 cases (36.9%) and 33 cases (18.8%) in the non-anxiety group, the anxiety tendency group and the anxiety group, respectively. The duration of disease in the anxiety group [(43.4±15.1) months] was significantly longer than that in the anxiety tendency group [(27.2±5.3) months] and the non-anxiety group [(19.6±3.5) months], with statistically significant differences (both P<0.05). The proportion of female patients in the anxiety group [81.8% (27/33)] and anxiety tendency group [75.4% (47/65)] was significantly higher than that in the non-anxiety group [57.7% (45/78)], and the differences were statistically significant (both P<0.05). The proportion of patients with emotional disorders [12.1% (4/33) vs 2.6% (2/78)], stress [15.1% (5/33) vs 3.9% (3/78)], and sleep disorders [48.5% (16/33) vs 23.1% (18/78)] in the anxiety group was significantly higher than that in the non-anxiety group (all P<0.05). The proportion of patients only had sleep disorders in the anxiety tendency group [38.5% (25/65) vs 23.1% (18/78)] was higher than that in the non-anxiety group, with a statistically significant difference (P<0.05). The results of multivariate ordered logistic regression analysis showed that sleep disorders werethe most significant factor affecting anxiety and anxiety tendency in tinnitus patients (OR=2.667, 95%CI: 1.451-4.909, P=0.002). Conclusion: A significant proportion of tinnitus patients exhibit anxiety and anxiety tendency, and sleep disorders play a major role in the development of anxiety and anxiety tendencies in tinnitus patients.

[Learning curve for a five-step procedure, transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction].

Objective: To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction. Methods: In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M(Q1, Q3) and the Mann-Whitney U test was used for inter group comparison. Results: The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x3-4.4757x2+164.97x-264.4 (P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor (P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups (P=0.238). Conclusion: Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

Standardized IETA criteria enhance accuracy of junior and intermediate ultrasound radiologists in diagnosing malignant endometrial and intrauterine lesions.

OBJECTIVES: To transform the standardized descriptions of the ultrasound characteristics of endometrial and intrauterine lesions devised by the International Endometrial Tumor Analysis (IETA) group into a practical scoring method and to investigate whether application of this method enhances the diagnostic accuracy of ultrasound radiologists with different levels of experience in detecting malignancy compared with subjective assessment. METHODS: This was a retrospective study of 855 patients with endometrial and/or intrauterine lesions, who were divided into a training (n = 600) and a validation (n = 255) set. Ultrasound radiologists with varying levels of experience (expert, intermediate and junior) evaluated all lesions by subjective assessment and according to IETA rules. Using IETA rules, the experts identified signs of malignancy in the training set, assigned scores for each indicator and validated the scoring method in the validation set. The intermediate-level and junior ultrasound radiologists reassessed the malignancy of the lesions using the IETA scoring method and compared their classifications with those made previously by subjective assessment. Postsurgical pathological evaluation was used as the reference standard. RESULTS: Using subjective assessment, the experts demonstrated the highest level of diagnostic accuracy, with a sensitivity of 85.0%, specificity of 94.3% and an area under the receiver-operating-characteristics curve (AUC) of 0.897. Applying the IETA scoring method (comprising eight ultrasound characteristics that contributed to the total score) with a threshold of > 25 points for the diagnosis of malignancy achieved a sensitivity of 84.7%, specificity of 94.7% and AUC of 0.9533 in the training set, with similar performance in the validation set, when performed by experts. Using the IETA scoring method, both junior and intermediate ultrasound radiologists showed improvement in sensitivity (from 55.5% to 74.8% and from 70.2% to 77.1%, respectively), specificity (from 88.4% to 91.5% and from 87.4% to 92.2%, respectively) and AUC (from 0.704 to 0.827 and from 0.793 to 0.841, respectively) for diagnosing malignant lesions. CONCLUSIONS: The IETA scoring method exhibits high diagnostic efficacy for malignant endometrial and intrauterine lesions. This method compensates for the lack of experience among junior and intermediate-level ultrasound radiologists, enhancing their diagnostic skill to a level nearing that of experienced senior ultrasound radiologists. Further research is essential to validate the practicality of implementing this method and to confirm its clinical value. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion.

Chimeric antigen receptor-modified T cell (CAR-T) immunotherapy has revolutionised blood cancer treatment. Parsing the genetic underpinnings of T cell quality and CAR-T efficacy is challenging. Transcriptomics inform CAR-T state, but the nature of dynamic transcription during activation hinders identification of transiently or minimally expressed genes, such as transcription factors, and over-emphasises effector and metabolism genes. Here we explore whether analyses of transcriptionally repressive and permissive histone methylation marks describe CAR-T cell functional states and therapeutic potential beyond transcriptomic analyses. Histone mark analyses improve identification of differences between naïve, central memory, and effector memory CD8 + T cell subsets of human origin, and CAR-T derived from these subsets. We find important differences between CAR-T manufactured from central memory cells of healthy donors and of patients. By examining CAR-T products from a clinical trial in lymphoma (NCT01865617), we find a novel association between the activity of the transcription factor KLF7 with in vivo CAR-T accumulation in patients and demonstrate that over-expression of KLF7 increases in vitro CAR-T proliferation and IL-2 production. In conclusion, histone marks provide a rich dataset for identification of functionally relevant genes not apparent by transcriptomics.

Dual-energy CT-based radiomics for predicting pathological grading of invasive lung adenocarcinoma.

AIMS: The purpose of the study was to build a radiomics model using Dual-energy CT (DECT) to predict pathological grading of invasive lung adenocarcinoma. MATERIALS AND METHODS: The retrospective study enrolled 107 patients (80 low-grade and 27 high-grade) with invasive lung adenocarcinoma before surgery. Clinical features, radiographic characteristics, and quantitative parameters were measured. Virtual monoenergetic images at 50kev and 150kev were reconstructed for extracting DECT radiomics features. To select features for constructing models, Pearson's correlation analysis, intraclass correlation coefficients, and least absolute shrinkage and selection operator penalized logistic regression were performed. Four models, including the DECT radiomics model, the clinical-DECT model, the conventional CT radiomics model, and the mixed model, were established. Area under the curve (AUC) and decision curve analysis were used to measure the performance and the clinical value of the models. RESULTS: The radiomics model based on DECT exhibited outstanding performance in predicting tumor differentiation, with an AUC of 0.997 and 0.743 in the training and testing sets, respectively. Incorporating tumor density, lobulation, and effective atomic number at AP, the clinical-DECT model showed a comparable performance with an AUC of 0.836 in both the training and testing sets. In comparison to the conventional CT radiomics model (AUC of 0.998 in the training and 0.529 in the testing set) and the mixed model (AUC of 0.988 in the training and 0.707 in the testing set), the DECT radiomics model demonstrated a greater AUC value and provided patients with a more significant net benefit in the testing set. CONCLUSIONS: In contrast to the conventional CT radiomics model, the DECT radiomics model produced greater predictive performance in pathological grading of invasive lung adenocarcinoma.

[Relationship between maternal and fetal ERAP-1 gene polymorphism and pre-eclampsia].

Objective: To investigate the relationship between the polymorphism of endoplasmic reticulum aminopeptidase 1 (ERAP-1) gene and the occurrence of pre-eclampsia (PE). Methods: A case-control study was conducted in Beijing Obstetrics and Gynecology Hospital from October 2018 to October 2021. A total of 51 PE pregnant women with onset gestational age<34 weeks were selected as the PE group, and 48 normal pregnant women during the same period were selected as the control group. Venous blood samples were collected from the pregnant women before delivery and umbilical cord within 5 minutes after delivery. Single nucleotide polymorphisms (SNP) of ERAP-1 gene in the pregnant women and their fetus were detected by next-generation sequencing. Univariate analysis and multivariate logistic regression analysis were used to analyze all the SNP loci and alleles detected in the two groups, and the significant SNP were screened. Results: (1) A total of 13 target SNP loci of maternal ERAP-1 gene were selected by univariate analysis. Among them, the frequency distribution of genotypes at 96096828, 96121524, 96121715, 96122260 and 96122281 showed statistically significant differences between PE group and control group (all P<0.05). Multivariate logistic regression analysis showed that the risk of PE in pregnant women with TC genotype at locus 96121524 was 2.002 times higher than those with TT genotype (95%CI: 0.687-5.831, P=0.020). (2) A total of 4 target SNP loci of ERAP-1 gene in fetal were selected by univariate analysis, and there was no statistical significance in gene polymorphism of the 4 loci between PE group and control group (all P>0.05). Multivariate logistic regression analysis showed that the risk of PE in fetus with genotype AA at locus 96121406 was 0.236 times that of fetus with genotype GG (95%CI: 0.055-1.025, P=0.016). Conclusion: ERAP-1 gene with TC genotype at 96121524 in the mother and GG genotype at 96121406 in the fetus might be related to the incidence of PE.

[Clinicopathological features of primary mucosal CD30-positive T-cell lymphoproliferative disorders].

Objective: To investigate the clinicopathological features and differential diagnosis of primary mucosal CD30-positive T-cell lymphoproliferative disorders (pmCD30+TLPD). Methods: Eight cases of pmCD30+TLPD diagnosed from 2013 to 2023 at the Department of Pathology, Beijing Friendship Hospital Affiliated to Capital Medical University and Beijing Ludaopei Hospital were retrospectively collected. The immunophenotype, EBV infection status and T-cell receptor (TCR) clonability of tumor cells were examined. The clinicopathological features were analyzed and related literatures were reviewed. Results: There were 5 females and 3 males, aged 28 to 73 years, without B symptoms, lack of trauma and autoimmune diseases. Seven cases occurred in oral mucosa and one in anal canal mucosa. Submucosal nodules with ulcerations were presented in all cases except one, which only submucosal nodule. Morphologically, there was different distribution of allotypic lymphocytes in inflammatory background. Four cases showed "kidney-shaped", "embryonic" and "horseshoe-shaped" cells, and one case resembled Hodgkin and Reed/Sternberg (HRS) cells. Allotypic lymphocytes expressed CD3 (7/8), CD4+/CD8-(7/8) and CD4-/CD8-(1/8). CD30 was uniformly strongly positive while ALK and CD56 were negative. In situ hybridization of EBER was negative in five cases (5/5). Clonal TCR gene rearrangement was positive in two cases. Four patients did not receive radiotherapy or chemotherapy. All the seven patients survived without disease except one died due to concurrent leukopenia. Conclusions: pmCD30+TLPD had a broad morphological spectrum and could be easily confused with primary cutaneous CD30+TLPD and systemic ALK-negative anaplastic large cell lymphoma involving mucosa, which may lead to misdiagnosis. Although the majority of the cases had a favorable prognosis, a few cases relapsed or progressed to lymphoma.

Strong and consistent effects of waterbird composition on HPAI H5 occurrences across Europe.

Since 2014, highly pathogenic avian influenza (HPAI) H5 viruses of clade 2.3.4.4 have been dominating the outbreaks across Europe, causing massive deaths among poultry and wild birds. However, the factors shaping these broad-scale outbreak patterns, especially those related to waterbird community composition, remain unclear. In particular, we do not know whether these risk factors differ from those of other H5 clades. Addressing this knowledge gap is important for predicting and preventing future HPAI outbreaks. Using extensive waterbird survey datasets from about 6883 sites, we here explored the effect of waterbird community composition on HPAI H5Nx (clade 2.3.4.4) spatial patterns in the 2016/2017 and 2020/2021 epidemics in Europe, and compared it with the 2005/2006 HPAI H5N1 (clade 2.2) epidemic. We showed that HPAI H5 occurrences in wild birds in the three epidemics were strongly associated with very similar waterbird community attributes, which suggested that, in nature, similar interspecific transmission processes operate between the HPAI H5 subtypes or clades. Importantly, community phylogenetic diversity consistently showed a negative association with H5 occurrence in all three epidemics, suggesting a dilution effect of phylogenetic diversity. In contrast, waterbird community variables showed much weaker associations with HPAI H5Nx occurrence in poultry. Our results demonstrate that models based on previous epidemics can predict future HPAI H5 patterns in wild birds, implying that it is important to include waterbird community factors in future HPAI studies to predict outbreaks and improve surveillance activities.

Channel utilization of media access control protocols for underwater acoustic networks with propagation delay and mobilitya).

This paper investigates the impact of mobility on underwater acoustic communication networks in which the propagation delay is comparable to or larger than the packet duration. An underwater acoustic wireless network, consisting of static and mobile nodes, is studied for its link-layer channel utilization. Synchronous and asynchronous media access control (MAC) protocols are employed with ALOHA, TDMA (time-division multiple access), and artificial intelligence (AI) agent nodes. The simulation results of a multi-node network show that the asynchronous MAC protocols achieve up to 6.66× higher channel utilization than synchronous protocols by allowing time slots to be shorter than the maximum propagation delay among nodes and permitting asynchronous transmission time. The high mobility of a few mobile nodes also favors asynchronous protocols and increases the overall channel utilization. However, node mobility causes more difficulties for the AI node to learn the environment, which may be ineffective to achieve higher gains in channel utilization.

Efficacy and safety of total glucosides of paeony in treating primary Sjögren's syndrome: a propensity-matched study.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of total glucosides of paeony (TGP) in patients with primary Sjögren's syndrome (pSS). PATIENTS AND METHODS: This study included 236 patients with pSS, including 118 TGP users and 118 non-users. Propensity score matching and Binary logistic regression analyses were used to minimize confounding factors and determine the association between TGP treatment and clinical variables. RESULTS: The baseline indexes of TGP users and non-users were basically the same. The median time of follow-up in the two groups was also similar (p < 0.05). Compared with non-users, TGP users showed higher rates of improvement in dry mouth and eyes and musculoskeletal involvement, as well as more significant reductions in serum alanine aminotransferase (ALT) and direct bilirubin (DBIL) levels after treatment. Logistic regression confirmed that the use of TGP was negatively correlated with the increase of ALT and DBIL in pSS patients, and the reduction in these variables was more pronounced after 2 years of treatment. The incidence of adverse reactions in the TGP users was 11.9%, which was compatible with those in non-users. CONCLUSIONS: TGP is often a safe option for treating pSS patients with musculoskeletal features and abnormal ALT levels. Besides, it can help improve dry mouth and dry eyes and decrease DBIL levels.

[Arrhythmias and electrocardiographic characteristics in cancer patients treated with immune checkpoint inhibitors].

Objective: To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs). Methods: This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes. Results: A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment (P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions: The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.

[Clinical analysis of 80 patients with oblique vaginal septum syndrome].

Objective: To investigate the clinical features, diagnosis and treatment of oblique vaginal septum syndrome (OVSS). Methods: The clinical data of 80 patients with OVSS admitted to The Second Hospital of Hebei Medical University from July 2005 to July 2023 were retrospectively analyzed. According to the classification system of OVSS proposed by Female Genital Anomalies Study Group, Chinese Obstetricians and Gynecologists Association in 2021, the patients were divided into four groups. The clinical manifestations, accompanied urinary system abnormalities, diagnosis and treatment methods and treatment outcomes were observed. Results: According to the above classification system, among the 80 patients with OVSS, 35 patients (44%, 35/80) were categorized as type Ⅰ, 33 patients (41%, 33/80) were categorized as type Ⅱ, 2 patients (3%, 2/80) were categorized as type Ⅲ and 10 patients (13%, 10/80) were categorized as type Ⅳ. The main onset symptom of patients was periodic abdominal pain (70%, 56/80), vaginal bleeding (20%, 16/80), dysuria or fecal impaction (15%, 12/80), vaginal mucopurulent discharge (10%, 8/80). The morbidity of combined urinary system abnormalities was 88% (70/80), and the most common urinary system abnormality was ipsilateral renal agenesis (81%, 65/80). Bilateral kidneys were normal in 13% (10/80) patients, and 6% (5/80) were combined with other urinary system abnormalities. A total of 74 patients underwent vaginal oblique septectomy or septum excision. Five of the 10 patients with type Ⅳ underwent hysterectomy on the cervical atresia side, 4 patients received hysteroscopy combined with cervicoplasty+oblique septotomy or septum excision, and one patient selected delayed menstruation. Two patients underwent laparoscopic resection of the dysplasia kidney and ectopic ureter which opening to the vagina. Eleven patients with endometriosis cyst, hydrosalpinx or empyema underwent laparoscopic surgery. Conclusions: The main symptom of type Ⅰ and Ⅳ patients is abdominal pain, while the main symptom of type Ⅱ and Ⅲ patients is bleeding. Magnetic resonance imaging (MRI) has advantages in the evaluation of complex OVSS, and MRI is recommended before operation to exclude other axial reproductive tract dysplasia and complex urinary system dysplasia. If there is leakage of urine, vaginal discharge or complex deformity, it is necessary to multidisciplinary discussion and formulate a reasonable surgical plan. The first treatment is related to the prognosis of patients especially children, and should be highly valued.