Objective:To explore the correlation of different HBV DNA loads with peripheral blood lymphocyte subsets and interleukin-6 (IL-6) in patients with chronic hepatitis B.Methods:A cross-sectional study was conducted. A total of 519 patients with chronic hepatitis B admitted to the Fifth Medical Center of the General Hospital of the People′s Liberation Army from April 2019 to June 2024 were included. The patients were divided into high, medium, and low viral load groups and a negative group based on HBV DNA load. Another 100 healthy individuals who underwent physical examinations during the same period were recruited as the control group. The quantities of peripheral blood lymphocyte subsets and IL-6 levels were compared among the groups. Meanwhile, alanine aminotransferase (ALT) levels were recorded and compared among the groups. The correlation of HBV DNA levels with lymphocyte subsets and IL-6 was analyzed using Pearson correlation analysis.Results:HBV DNA loads were negatively correlated with the counts of CD3 +, CD4 +, CD8 +, CD19 +, and CD56 + lymphocyte subsets (correlation coefficients r were -0.483, -0.508, -0.524, -0.573, and -0.561, respectively; all P<0.001) and positively correlated with IL-6 levels ( r=0.862, P<0.05). Compared with the control group, the counts of each lymphocyte subset were higher in the high, medium, and low viral load groups ( P<0.05). In the HBV DNA-negative chronic hepatitis B group, the counts of CD8 + and CD19 + lymphocyte subsets were significantly higher [712.32(526.00,898.64) and 495.62(345.74,645.50) cells/μl] than those in the control group [612.10(479.89,744.31) and 470.32 (396.00,544.64) cells/μl] ( P<0.05). Conclusion:The degree of HBV replication activity in patients with chronic hepatitis B is associated with the immune status of the body, and negatively correlated with the quantities of lymphocyte subsets and positively correlated with IL-6 levels.

[Objective]To explore the distribution patterns and correlations of pet-related cat/dog dander allergens and mold allergens in patients with allergic diseases,providing evidence for individualized diagnosis,treatment,and prevention strategies.[Methods]A retrospective analysis was conducted on 798 patients diagnosed with allergic diseases at the Third Affiliated Hospital of Sun Yat-sen University between April 2021 and October 2023.All patients underwent UniCAP platform testing for specific immunoglobulin E(sIgE)levels against cat dander,dog dander,and mold mix(mx1/mx2),alongside total IgE(tIgE)quantification.Descriptive statistics,Mann-Whitney U tests,and chi-square analyses were employed to evaluate allergen distribution and interrelationships.[Results]Among the 798 patients(395 males,403 females,ratio 1:1.02),their ages ranged from 0.67 to 69 years(median 14 years,IQR 6-29).A total of 63.2％(504/798)had a single allergic disease,with allergic rhinitis(AR,49.2％)being the most common.The remaining 36.8％(294/798)had≥2 allergic diseases,with AR combined with atopic dermatitis(AD,10.7％)as the predominant comorbidity.The positivity rate for cat/dog dander sIgE was 24.1％(192/798),with a significantly higher prevalence in females(30.8％)than males(16.7％,P<0.05).Cat dander sensitization increased with age in patients under 18 years.Among positive cases,cat dander sIgE level 2 was most frequent(25.9％),while dog dander sIgE level 1 predominated(55％).Patients with cat dander sIgE levels 4-6 had significantly higher tIgE than those with levels 1-3(P<0.05).The positivity rate for mold mix(mx1/mx2)sIgE was 7.4％(59/798),with mx2 as the primary sensitizer and level 2 being the most common.In mx2-positive patients,the cat/dog dander sIgE positivity rate(44.8％)was significantly higher than that in mx2-negative patients(17.9％,P<0.05),and tIgE levels were also higher(P<0.05).[Conclusion]Cat dander sensitization increases with age in children.Cat/dog dander and mold allergens are closely linked to AR and AR combined with AD.Synergistic correlations exist between cat/dog dander sIgE and mold mx2 sIgE.Combined detection of these allergens is critical for precision diagnosis and management of pet-related allergic diseases.

Objective:To explore the correlation of different HBV DNA loads with peripheral blood lymphocyte subsets and interleukin-6 (IL-6) in patients with chronic hepatitis B.Methods:A cross-sectional study was conducted. A total of 519 patients with chronic hepatitis B admitted to the Fifth Medical Center of the General Hospital of the People′s Liberation Army from April 2019 to June 2024 were included. The patients were divided into high, medium, and low viral load groups and a negative group based on HBV DNA load. Another 100 healthy individuals who underwent physical examinations during the same period were recruited as the control group. The quantities of peripheral blood lymphocyte subsets and IL-6 levels were compared among the groups. Meanwhile, alanine aminotransferase (ALT) levels were recorded and compared among the groups. The correlation of HBV DNA levels with lymphocyte subsets and IL-6 was analyzed using Pearson correlation analysis.Results:HBV DNA loads were negatively correlated with the counts of CD3 +, CD4 +, CD8 +, CD19 +, and CD56 + lymphocyte subsets (correlation coefficients r were -0.483, -0.508, -0.524, -0.573, and -0.561, respectively; all P<0.001) and positively correlated with IL-6 levels ( r=0.862, P<0.05). Compared with the control group, the counts of each lymphocyte subset were higher in the high, medium, and low viral load groups ( P<0.05). In the HBV DNA-negative chronic hepatitis B group, the counts of CD8 + and CD19 + lymphocyte subsets were significantly higher [712.32(526.00,898.64) and 495.62(345.74,645.50) cells/μl] than those in the control group [612.10(479.89,744.31) and 470.32 (396.00,544.64) cells/μl] ( P<0.05). Conclusion:The degree of HBV replication activity in patients with chronic hepatitis B is associated with the immune status of the body, and negatively correlated with the quantities of lymphocyte subsets and positively correlated with IL-6 levels.

Objective:To evaluate the relationship between prognostic nutritional index (PNI) and risk of functional dependence in patients receiving maintenance hemodialysis (MHD).Methods:It was a cross-sectional survey study. The clinical data of MHD patients in the Second Affiliated Hospital of Soochow University from June to December 2023 were collected. The Katz and Lawton-Brody questionnaires were used to assess the functional status. The patients were divided into normal functional status group and functional dependence group, and the differences of the clinical data between the two groups were compared. Serum albumin and lymphocytes were used to determine PNI, and the patients were divided into four subgroups: Q1 group (PNI≤44.3), Q2 group (44.349.8) according to the quartile of PNI. Logistic regression analysis method was used to analyze the relationship between PNI and risk of functional dependence in MHD patients, and subgroup analysis was conducted. The receiver-operating characteristic (ROC) curve was used to assess the efficacy of PNI, serum albumin, and lymphocytes in predicting the risk of functional dependence in MHD patients.Results:A total of 206 MHD patients were included in this study, with age of (58.35±0.98) years old, and 132 (64.1%) males. There were 58 (28.2%) patients with diabetes, 179 (86.9%) patients with hypertension, and 36 (17.5%) patients with cardiovascular diseases. There were 95 (46.1%) patients developing functional dependence. Compared with normal functional status group, functional dependence group had higher age ( t=-6.87, P<0.001), proportion of diabetes ( χ2=6.58, P=0.010), and pulse pressure ( t=-3.17, P=0.002), and lower diastolic pressure ( t=3.88, P<0.001), serum creatinine ( t=3.44, P=0.001), serum albumin ( t=4.09, P<0.001) and PNI ( t=3.92, P<0.001). The incidence of functional dependence in PNI Q1 group (69.2%, 36/52) was significantly higher than those in Q2 group (49.0%, 25/51), Q3 group (34.0%, 18/53) and Q4 group (32.0%, 16/50), and the differences among groups were statistically significant (all P<0.05). Logistic regression analysis showed that after adjusting for confounding factors: age, diabetes, pulse pressure, and serum creatinine, the risk of functional dependence of PNI Q1 group was 3.217 folds higher than that in Q4 group ( OR=3.217, 95% CI 1.229-8.422, P=0.017). The risk probability model of PNI predicting the occurrence of functional dependence in MHD patients: logit (odds)=5.854-0.128 3×PNI. The area under the ROC curve ( AUC) for PNI predicting the risk of functional dependence in MHD patients was 0.66 (95% CI 0.58-0.73, P<0.001), slightly higher than that of serum albumin ( AUC=0.64, 95% CI 0.54-0.73, P<0.001). The optimal cutoff value of PNI predicting the occurrence of functional dependence was 46.15, with sensitivity of 72.07% and specificity of 57.89%. Conclusion:Low PNI is associated with high risk of functional dependence in MHD patients.

Nonalcoholic fatty liver disease(NAFLD)has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma.However,the pathogenesis of NAFLD remains unclear,and there is still a lack of specific treatment measures.Sterol regulatory element-binding proteins(SREBP)are an important nuclear transcription factor,which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol,fatty acids,and triglycerides,and therefore,SREBP are a target for the treatment of metabolic diseases.This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD.It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage.Therefore,excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD.In conclusion,SREBP is a promising therapeutic target for NAFLD;the molecular mechanism of SREBP in lipid metabolism is regulated by many factors,and these factors are being deeply explored and analyzed,which has an important clinical significance for the treatment of NAFLD.

Background::With an increasing proportion of multiparas, proper interpregnancy intervals (IPIs) are urgently needed. However, the association between IPIs and adverse perinatal outcomes has always been debated. This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.Methods::We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019. Multivariable Poisson models with restricted cubic splines were used. Each adverse outcome was analyzed separately in the overall model and stratified models. The stratified models included different categories of fertility policy periods (2014–2015, 2016–2017, and 2018–2019) and infant gestational age in previous pregnancy (<28 weeks, 28–36 weeks, and ≥37 weeks).Results::There were 781,731 pregnancies enrolled in this study. A short IPI (≤6 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.63 [1.55, 1.71] for vaginal delivery [VD] and 1.10 [1.03, 1.19] for cesarean section [CS]), low Apgar scores and small for gestational age (SGA), and a decreased risk of diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. A long IPI (≥60 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.18 [1.11, 1.26] for VD and 1.39 [1.32, 1.47] for CS), placenta previa, postpartum hemorrhage, diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes. The estimated risk of preterm birth, low Apgar scores, SGA, diabetes mellitus in pregnancy, and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.Conclusion::For pregnant women with shorter or longer IPIs, more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

Objective To explore the application and prospects of artificial intelligence (AI) in metabolic associated fatty liver disease (MAFLD) based on bibliometrics. Methods Relevant literature on the application of AI technology in MAFLD was retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was conducted using CiteSpace, VOSviewer, R package "bibliometrix", and online bibliometric analysis was platformed to identify hotspots and trends in this field. Results A total of 303 eligible articles were obtained. Since 2017, the number of papers in this field had experienced explosive growth. The United States was leading the research on the application of AI in MAFLD and was the most frequent participant in international cooperation. San Diego of University of California was the institution with the highest number of publications. Rohit Loomba was the author with the highest number of publications, having published 14 articles. The co-cited keyword clustering labels revealed 10 major clusters: digital image analysis, machine learning, computer-aided diagnosis, fibrosis stage, automated quantitative analysis, metaproteomics, non-invasive diagnosis, ultrasonography, electronic health records, and knowledge representation. Current research on the application of AI in MAFLD mainly focused on the diagnosis, differential diagnosis, and staging of MAFLD. Image recognition and analysis, intelligent assisted diagnosis, AI algorithms, and monitoring disease progression will be important research directions for AI in MAFLD. Conclusion Research on the application of AI in MAFLD is experiencing exponential growth. Given enormous potential and clinical application prospects of this field, the application of AI in MAFLD-related areas will remain a research hotspot in the future.

OBJECTIVE To explore the potential mechanism of action of Gexia zhuyu decoction in the intervention of metabolic-associated fatty liver disease(MAFLD)based on ferroptosis.METHODS With the help of network pharmacology,the central targets of Gexia zhuyu decoction intervening in ferroptosis of MAFLD were screened,then gene ontology,Kyoto Encyclopedia Gene and Genomes enrichment analysis and molecular docking were performed.Juvenile zebrafish with normal development at 3 d post-fertilization were randomly divided into control group,model group(5 mmol/L thioacetamide),magnesium isoglycyrrhizinate group(positive control,5 mg/mL),and Gexia zhuyu decoction low-,medium-and high-concentration groups(20,40,80 μg/mL,calculated by crude drugs).After cultured for 72 h,the contents of alanine transaminase(ALT),aspartate transaminase(AST),total cholesterol(TC),triglyceride(TG),malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),reactive oxygen species(ROS)and Fe2+were determined;the cellular structure of the liver tissues and hepatic steatosis were observed;the protein expression of silence information regulator 1(SIRT1),nuclear factor-erythroid 2-related factor 2(Nrf2)and glutathione peroxidase 4(GPX4)were detected.RESULTS The central targets of potential active ingredients of Gexia zhuyu decoction that act on ferroptosis in MAFLD included tumor proteins p53,SIRT1,Nrf2,etc.,which were enriched in biological processes such as positive/negative regulation of RNA polymerase n promoter transcription,cellular components such as nucleus and cytoplasm,molecular functions such as protein binding,as well as signaling pathways such as ferroptosis and the cancer pathway,and they might be tightly linked to the main active ingredients.Compared with model group,the contents of ALT,AST,TC,TG,MDA,ROS and Fe2+were all decreased significantly in each administration group,while the contents of SOD and GSH were increased significantly(P＜0.05);the pathological damage of liver tissue cells had improved,and the accumulation of liver lipids had decreased.The protein expressions of SIRT1,Nrf2 and GPX4 had been significantly upregulated(P＜0.05).CONCLUSIONS Gexia zhuyu decoction can regulate lipid metabolism,improve the level of oxidative stress,maintain Fe2+homeostasis,and inhibit the process of ferroptosis in juvenile zebrafish with MAFLD,and the above effects may be related to the activation of the SIRT1/Nrf2/GPX4 axis.

Objective:To study the correlation between the quartering of nerve root subsidence sign (NRS) and the cross-sectional area (CSA) of the narrow segment thecal sac in patients with lumbar spinal stenosis (LSS).Methods:The data of 203 LSS patients in the Fourth People′s Hospital of Hengshui from January 2020 to December 2021 were retrospectively analyzed. All patients underwent MRI cross sectional scanning. The patients were divided into positive type a group ( n=62), positive type b group ( n=32), positive type c group ( n=51), and negative group ( n=58) by NRS quartering method. The minimum CSA, median sagittal diameter (PAD), and lateral recess sagittal diameter of each group were compared. The correlation between NRS quartering classification and the minimum CSA and related indicators of lumbar spinal stenosis was analyzed. Results:The minimum CSA, PAD, and sagittal diameter of the lateral recess in the positive a group, positive b group, and positive c group were all smaller than those in the negative group, while the Visual Analogue Scale (VAS) score and Oswestry Disability Index (ODI) were higher than those in the negative group; The minimum CSA, PAD, and sagittal diameter of the lateral recess in the positive b type and positive c type groups were smaller than those in the positive a type group, while the VAS score and ODI index were higher than those in the positive a type group; The minimum CSA, PAD, and sagittal diameter of the lateral recess in the positive c type group were smaller than those in the positive b type group; The VAS score and ODI index were higher than those of the positive b type group; The differences were statistically significant (all P<0.05). 203 patients were divided into 54 normal cases, 58 mild stenosis cases, 49 moderate stenosis cases, and 42 severe stenosis cases based on the minimum CSA. The coincidence rate between negative NRS and minimal CSA diagnosis as normal was 94.44%(51/54), the coincidence rate between positive type a and minimal CSA diagnosis as mild stenosis was 84.48%(49/58), the coincidence rate between positive type b and minimal CSA diagnosis as moderate stenosis was 53.06%(26/49), and the coincidence rate between positive type c and minimal CSA diagnosis as severe stenosis was 90.48%(38/42). Using the kappa consistency test, the kappa value for quantitative diagnosis of minimum CSA stenosis in NRS and LSS patients was 0.743, indicating good consistency. The kappa values for quantitative diagnosis of NRS, sagittal diameter of lateral recess, and PAD stenosis were 0.271 and 0.335, with poor consistency. NRS typing was negatively correlated with CSA and PAD ( r=-0.723, -0.581, all P<0.001), and positively correlated with VAS score and ODI index ( r=0.473, 0.640, all P<0.001). Conclusions:The NRS quartering method has a good consistency in diagnosing the severity of LSS patients and the minimum CSA of stenosis segments, suggesting that the NRS quartering method can better reflect the degree of Spinal stenosis, which can not only be used as an auxiliary indicator for qualitative diagnosis of LSS, but also has a high value in quantitative diagnosis.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).